Aflatoxins are toxic secondary fungal metabolites that contaminate dietary staples in tropical regions; chronic high levels of exposure are common for many of the poorest populations. Observations in animals indicate that growth and/or food utilization are adversely affected by aflatoxins. This review highlights the development of validated exposure biomarkers and their use here to assess the role of aflatoxins in early life growth retardation. Aflatoxin exposure occurs in utero and continues in early infancy as weaning foods are introduced. Using aflatoxin-albumin exposure biomarkers, five major studies clearly demonstrate strong dose response relationships between exposure in utero and/or early infancy and growth retardation, identified by reduced birth weight and/or low HAZ and WAZ scores. The epidemiological studies include cross-sectional and longitudinal surveys, though aflatoxin reduction intervention studies are now required to further support these data and guide sustainable options to reduce the burden of exposure. The use of aflatoxin exposure biomarkers was essential in understanding the observational data reviewed and will likely be a critical monitor of the effectiveness of interventions to restrict aflatoxin exposure. Given that an estimated 4.5 billion individuals live in regions at risk of dietary contamination the public health concern cannot be over stated. 1. Introduction Fungal toxins, also known as mycotoxins, are frequent contaminants of dietary staples for much of the world. These potent dietary toxins are estimated to contaminate 25% of the world’s cereal crops [1] making exposure frequent among many populations. Among the hundreds of mycotoxins identified, those of major public health concern include aflatoxins produced from Aspergillus fungi and both the fumonisins and the trichothecenes (e.g., deoxynivalenol (DON), nivalenol, and T2-toxin) from Fusarium fungi. Aflatoxins and fumonisins tend to be more frequent contaminants of crops in hot and humid climates as in Central America, tropical Asia, and sub-Saharan Africa where staple foods such as maize and groundnuts (peanuts) are often contaminated. Trichothecenes tend to occur more frequently in more temperate regions including parts of Asia, Europe, and North and South America [1]. This review will focus on the toxicology of the aflatoxins, the need for the development of exposure biomarkers to improve our understanding of the etiology of aflatoxin driven chronic diseases, and specifically in this review the use of aflatoxin exposure biomarkers in revealing aflatoxins role in
References
[1]
CAST, “Potential economic costs of mycotoxins in the United States,” in Mycotoxins: Risks in Plant, Animal, and Human Systems, Task Force Report No. 139, pp. 136–142, Council for Agricultural Science and Technology, Ames, Iowa, USA, 2003.
[2]
B. Armbrecht, H. Wiseman, W. Shalkop, and J. Geleta, “Swine aflatoxicosis. I. An assessment of growth efficiency and other responses in growing pigs fed aflatoxin,” Environmental Physiology & Biochemistry, vol. 1, pp. 198–208, 1971.
[3]
W. L. Bryden, R. B. Cumming, and D. Balnave, “The influence of vitamin A status on the response of chickens to aflatoxin B1 and changes in liver lipid metabolism associated with aflatoxicosis,” British Journal of Nutrition, vol. 41, no. 3, pp. 529–540, 1979.
[4]
W. Butler and J. Wigglesworth, “The effects of aflatoxin B1 on the pregnant rat,” British Journal of Experimental Pathology, vol. 47, pp. 242–247, 1966.
[5]
Y. Dersjant-Li, M. W. A. Verstegen, and W. J. J. Gerrits, “The impact of low concentrations of aflatoxin, deoxynivalenol or fumonisin in diets on growing pigs and poultry,” Nutrition Research Reviews, vol. 16, no. 2, pp. 223–239, 2003.
[6]
J. A. Doerr, W. E. Huff, C. J. Wabeck, G. W. Chaloupka, J. D. May, and J. W. Merkley, “Effects of low level chronic aflatoxicosis in broiler chickens,” Poultry Science, vol. 62, no. 10, pp. 1971–1977, 1983.
[7]
T. S. Edrington, R. B. Harvey, and L. F. Kubena, “Effect of aflatoxin in growing lambs fed ruminally degradable or escape protein sources,” Journal of Animal Science, vol. 72, no. 5, pp. 1274–1281, 1994.
[8]
S. Gratz, M. T?ubel, R. O. Juvonen et al., “Lactobacillus rhamnosus strain GG modulates intestinal absorption, fecal excretion, and toxicily of aflatoxin B1 in rats,” Applied and Environmental Microbiology, vol. 72, no. 11, pp. 7398–7400, 2006.
[9]
R. B. Harvey, W. E. Huff, L. F. Kubena, and T. D. Phillips, “Evaluation of diets contaminated with aflatoxin and ochratoxin fed to growing pigs,” The American Journal of Veterinary Research, vol. 50, no. 8, pp. 1400–1405, 1989.
[10]
W. E. Huff, “Evaluation of tibial dyschondroplasia during aflatoxicosis and feed restriction in young broiler chickens,” Poultry Science, vol. 59, no. 5, pp. 991–995, 1980.
[11]
A. C. Keyl and A. N. Booth, “Aflatoxin effects in livestock,” Journal of the American Oil Chemists' Society, vol. 48, no. 10, pp. 599–604, 1971.
[12]
T. Kihara, T. Matsuo, M. Sakamoto, Y. Yasuda, Y. Yamamoto, and T. Tanimura, “Effects of prenatal aflatoxin B1 exposure on behaviors of rat offspring,” Toxicological Sciences, vol. 53, no. 2, pp. 392–399, 2000.
[13]
D. E. Marin, I. Taranu, R. P. Bunaciu et al., “Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin,” Journal of Animal Science, vol. 80, no. 5, pp. 1250–1257, 2002.
[14]
E. Mocchegiani, A. Corradi, L. Santarelli et al., “Zinc, thymic endocrine activity and mitogen responsiveness (PHA) in piglets exposed to maternal aflatoxicosis B1 and G1,” Veterinary Immunology and Immunopathology, vol. 62, no. 3, pp. 245–260, 1998.
[15]
V. S. Panangala, J. J. Giambrone, and U. L. Diener, “Effects of aflatoxin on the growth performance and immune responses of weanling swine,” The American Journal of Veterinary Research, vol. 47, no. 9, pp. 2062–2067, 1986.
[16]
G. M. Randall and F. H. Bird, “The effect of exercise on the toxicity of aflatoxin B1 in chickens,” Poultry Science, vol. 58, no. 5, pp. 1284–1288, 1979.
[17]
R. E. Schmidt and R. J. Panciera, “Effects of aflatoxin on pregnant hamsters and hamster foetuses,” Journal of Comparative Pathology, vol. 90, no. 3, pp. 339–347, 1980.
[18]
L. L. Southern and A. J. Clawson, “Effects of aflatoxins on finishing swine,” Journal of Animal Science, vol. 49, no. 4, pp. 1006–1011, 1979.
[19]
IARC, Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. IARC Monogr Eval Carcinog Risks Hum, vol. 82, IARC, Lyon, France, 2002.
[20]
J. D. Miller, “Fungi and mycotoxins in grain: implications for stored product research,” Journal of Stored Products Research, vol. 31, no. 1, pp. 1–16, 1995.
[21]
P. C. Turner, B. Flannery, C. Isitt, M. Ali, and J. Pestka, “The role of biomarkers in evaluating human health concerns from fungal contaminants in food,” Nutrition Research Reviews, vol. 25, no. 1, pp. 162–179, 2012.
[22]
P. C. Turner, L. van der Westhuizen, and A. N. Da Costa, “Biomarkers of exposure: mycotoxins—aflatoxin, deoxynivalenol and fumonisins,” in Biomarkers and Human Biomonitoring, L. E. Knudsen and D. F. Merlo, Eds., Royal Society of Chemistry, Cambridge, UK, 2012.
[23]
C. P. Wild and P. C. Turner, “Exposure biomarkers in chemoprevention studies of liver cancer,” in Biomarkers in Cancer Chemoprevention, A. B. Millar, H. Bartsch, P. Boffetta, L. Dragsted, and H. Vainio, Eds., IARC Scientific Publications No. 154, pp. 215–222, 2001.
[24]
C. P. Wild and P. C. Turner, “The toxicology of aflatoxins as a basis for public health decisions,” Mutagenesis, vol. 17, no. 6, pp. 471–481, 2002.
[25]
Y. Y. Gong, L. Torres-Sanchez, L. Lopez-Carrillo et al., “Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population,” Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 3, pp. 688–694, 2008.
[26]
IARC, Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins, vol. 56, IARC, Lyon, France, 1993.
[27]
J. D. Groopman, C. P. Wild, J. Hasler, C. Junshi, G. N. Wogan, and T. W. Kensler, “Molecular epidemiology of aflatoxin exposures: validation of aflatoxin-N7-guanine levels in urine as a biomarker in experimental rat models and humans,” Environmental Health Perspectives, vol. 99, pp. 107–113, 1993.
[28]
F. P. Guengerich, Y. F. Ueng, B. R. Kim et al., “Activation of toxic chemicals by cytochrome P450 enzymes: regio- and stereoselective oxidation of aflatoxin B1,” Advances in Experimental Medicine and Biology, vol. 387, pp. 7–15, 1996.
[29]
F. P. Guengerich, W. W. Johnson, T. Shimada, Y. F. Ueng, H. Yamazaki, and S. Langouet, “Activation and detoxification of aflatoxin B1,” Mutation Research, vol. 402, pp. 121–128, 1998.
[30]
E. P. Gallagher, K. L. Kunze, P. L. Stapleton, and D. L. Eaton, “The kinetics of aflatoxin B1 oxidation by human cDNA-expressed and human liver microsomal cytochromes P450 1A2 and 3A4,” Toxicology and Applied Pharmacology, vol. 141, no. 2, pp. 595–606, 1996.
[31]
M. Abdel-Wahab, M. Mostafa, M. Sabry, M. El-Farrash, and T. Yousef, “Aflatoxins as a risk factor for hepatocellular carcinoma in Egypt, Mansoura Gastroenterology Center Study,” Hepato-Gastroenterology, vol. 55, no. 86-87, pp. 1754–1759, 2008.
[32]
Y. M. Abdulrazzaq, N. Osman, and A. Ibrahim, “Fetal exposure to aflatoxins in the United Arab Emirates,” Annals of Tropical Paediatrics, vol. 22, no. 1, pp. 3–9, 2002.
[33]
Y. M. Abdulrazzaq, N. Osman, Z. M. Yousif, and O. Trad, “Morbidity in neonates of mothers who have ingested aflatoxins,” Annals of Tropical Paediatrics, vol. 24, no. 2, pp. 145–151, 2004.
[34]
E. O. Abulu, N. Uriah, H. S. Aigbefo, P. A. Oboh, and D. E. Agbonlahor, “Preliminary investigation on aflatoxin in cord blood of jaundiced neonates,” West African Journal of Medicine, vol. 17, no. 3, pp. 184–187, 1998.
[35]
N. A. Ankrah, T. Rikimaru, and F. A. Ekuban, “Observations on aflatoxins and the liver status of Ghanaian subjects,” East African Medical Journal, vol. 71, no. 11, pp. 739–741, 1994.
[36]
T. C. Chao, D. Lo, B. C. Bloodworth, R. Gunasegaram, T. H. Koh, and H. S. Ng, “Aflatoxin exposure in Singapore: blood aflatoxin levels in normal subjects, hepatitis B virus carriers and primary hepatocellular carcinoma patients,” Medicine, Science and the Law, vol. 34, no. 4, pp. 289–298, 1994.
[37]
J. B. S. Coulter, S. M. Lamplugh, and G. I. Suliman, “Aflatoxins in human breast milk,” Annals of Tropical Paediatrics, vol. 4, no. 2, pp. 61–66, 1984.
[38]
J. B. S. Coulter, R. G. Hendrickse, S. M. Lamplugh et al., “Aflatoxins and kwashiorkor: clinical studies in Sudanese children,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 80, no. 6, pp. 945–951, 1986.
[39]
D. W. Denning, J. K. Onwubalili, A. P. Wilkinson, and M. R. A. Morgan, “Measurement of aflatoxin in Nigerian sera by enzyme-linked immunosorbent assay,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 82, no. 1, pp. 169–171, 1988.
[40]
D. W. Denning, J. A. Sykes, A. P. Wilkinson, and M. R. A. Morgan, “High serum concentrations of aflatoxin in Nepal as measured by enzyme-linked immunosorbent serum assay,” Human and Experimental Toxicology, vol. 9, no. 3, pp. 143–146, 1990.
[41]
H. R. de Vries, S. M. Maxwell, and R. G. Hendrickse, “Foetal and neonatal exposure to aflatoxins,” Acta Paediatrica Scandinavica, vol. 78, no. 3, pp. 373–378, 1989.
[42]
H. R. de Vries, S. M. Maxwell, and R. G. Hendrickse, “Aflatoxin excretion in children with kwashiorkor or marasmic kwashiorkor—a clinical investigation,” Mycopathologia, vol. 110, no. 1, pp. 1–9, 1990.
[43]
N. L. Hatem, H. M. A. Hassab, E. M. Abd Al-Rahman, S. A. El-Deeb, and R. L. El-Sayed Ahmed, “Prevalence of aflatoxins in blood and urine of Egyptian infants with protein-energy malnutrion,” Food and Nutrition Bulletin, vol. 26, no. 1, pp. 49–56, 2005.
[44]
R. G. Hendrickse, “The influence of aflatoxins on child health in the tropics with particular reference to kwashiorkor,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 78, no. 4, pp. 427–435, 1984.
[45]
C. López, L. Ramos, L. Bulacio, S. Ramadán, and F. Rodríguez, “Aflatoxin B1 content in patients with hepatic diseases,” Medicina, vol. 62, no. 4, pp. 313–316, 2002.
[46]
D. Mizrak, B. Engin, F. O. Onder, et al., “Aflatoxin exposure in viral hepatitis patients in Turkey,” The Turkish Journal of Gastroenterology, vol. 20, no. 3, pp. 192–197, 2009.
[47]
G. C. Onyemelukwe and G. Ogbadu, “Aflatoxin levels in sera of healthy first time rural blood donors: preliminary report,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 75, no. 6, pp. 780–782, 1981.
[48]
H. A. Sayed, A. El Ayyat, H. El Dusoki et al., “A cross sectional study of hepatitis B, C, some trace elements, heavy metals, aflatoxin B1 and schistosomiasis in a rural population, Egypt,” The Journal of the Egyptian Public Health Association, vol. 80, no. 3-4, pp. 355–388, 2005.
[49]
B. O. Shouman, D. El Morsi, S. Shabaan, A. H. Abdel-Hamid, and A. Mehrim, “Aflatoxin B1 level in relation to child's feeding and growth,” Indian Journal of Pediatrics, vol. 79, no. 1, pp. 56–61, 2012.
[50]
C. K. Tan, D. S. Lo, N. M. Law, H. S. Ng, and T. C. Chao, “Blood aflatoxin levels in patients with hepatocellular carcinoma in Singapore,” Singapore Medical Journal, vol. 36, no. 6, pp. 612–614, 1995.
[51]
S. Tsuboi, T. Nakagawa, and M. Tomita, “Detection of aflatoxin B1 in serum samples of male Japanese subjects by radioimmunoassay and high-performance liquid chromatography,” Cancer Research, vol. 44, no. 3, pp. 1231–1234, 1984.
[52]
Y. M. Abdulrazzaq, N. Osman, Z. M. Yousif, and S. Al-Falahi, “Aflatoxin M1 in breast-milk of UAE women,” Annals of Tropical Paediatrics, vol. 23, no. 3, pp. 173–179, 2003.
[53]
O. Adejumo, O. Atanda, A. Raiola, Y. Somorin, R. Bandyopadhyay, and A. Ritieni, “Correlation between aflatoxin M1 content of breast milk, dietary exposure to aflatoxin B1 and socioeconomic status of lactating mothers in Ogun State, Nigeria,” Food and Chemical Toxicology, vol. 56, pp. 171–177, 2013.
[54]
W. A. Anwar, H. M. Khaled, H. A. Amra, H. El-Nezami, and C. A. Loffredo, “Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention,” Mutation Research, vol. 659, no. 1-2, pp. 176–184, 2008.
[55]
H. S. El-Nezami, G. I. Nicoletti, G. E. Neal, D. C. Donohue, and J. T. Ahokas, “Aflatoxin M1 in human breast milk samples from Victoria, Australia and Thailand,” Food and Chemical Toxicology, vol. 33, no. 3, pp. 173–179, 1995.
[56]
A. A. El-Sayed, E. A. Soher, and A. Neamat-Allah, “Human exposure to mycotoxins in Egypt,” Mycotoxin Research, vol. 18, no. 1, pp. 23–30, 2002.
[57]
W. F. El-Tras, N. N. El-Kady, and A. A. Tayel, “Infants exposure to aflatoxin M1 as a novel foodborne zoonosis,” Food and Chemical Toxicology, vol. 49, no. 11, pp. 2816–2819, 2011.
[58]
A. O. Elzupir, A. R. A. Abas, M. H. Fadul et al., “Aflatoxin M1 in breast milk of nursing Sudanese mothers,” Mycotoxin Research, vol. 28, no. 2, pp. 131–134, 2012.
[59]
S. A. Ghiasain and A. H. Maghsood, “Infants' exposure to aflatoxin M1 from Mother's breast milk in Iran,” Iranian Journal of Public Health, vol. 41, no. 3, pp. 119–126, 2012.
[60]
A. Gürbay, S. A. Sabuncuo?lu, G. Girgin et al., “Exposure of newborns to aflatoxin M1 and B1 from mothers' breast milk in Ankara, Turkey,” Food and Chemical Toxicology, vol. 48, no. 1, pp. 314–319, 2010.
[61]
Y. Keskin, R. Ba?kaya, S. Karsli, T. Yurdun, and O. ?zyaral, “Detection of aflatoxin M1 in human breast milk and raw Cow's milk in Istanbul, Turkey,” Journal of Food Protection, vol. 72, no. 4, pp. 885–889, 2009.
[62]
R. Mahdavi, L. Nikniaz, S. R. Arefhosseini, and M. V. Jabbari, “Determination of aflatoxin M1 in breast milk samples in Tabriz-Iran,” Maternal and Child Health Journal, vol. 14, no. 1, pp. 141–145, 2010.
[63]
S. S. Omar, “Incidence of aflatoxin M1 in human and animal milk in Jordan,” Journal of Toxicology and Environmental Health, vol. 75, no. 22-23, pp. 1404–1409, 2012.
[64]
N. Polychronaki, P. C. Turner, H. Mykk?nen et al., “Determinants of aflatoxin M1 in breast milk in a selected group of Egyptian mothers,” Food Additives and Contaminants, vol. 23, no. 7, pp. 700–708, 2006.
[65]
N. Polychronaki, R. M. West, P. C. Turner et al., “A longitudinal assessment of aflatoxin M1 excretion in breast milk of selected Egyptian mothers,” Food and Chemical Toxicology, vol. 45, no. 7, pp. 1210–1215, 2007.
[66]
A. M. Saad, A. M. Abdelgadir, and M. O. Moss, “Aflatoxin in human and camel milk in Abu Dhabi, United Arab Emirates,” Mycotoxin Research, vol. 5, no. 2, pp. 57–60, 1989.
[67]
A. M. Saad, A. M. Abdelgadir, and M. O. Moss, “Exposure of infants to affatoxin M1 from mothers' breast milk in Abu Dbabi, UAE,” Food Additives and Contaminants, vol. 12, no. 2, pp. 255–261, 1995.
[68]
R. H. Tomerak, H. H. Shaban, O. A. Khalafallah, and M. N. El Shazly, “Assessment of exposure of Egyptian infants to aflatoxin M1 through breast milk,” The Journal of the Egyptian Public Health Association, vol. 86, no. 3-4, pp. 51–55, 2011.
[69]
A. Zarba, C. P. Wild, A. J. Hall, R. Montesano, G. J. Hudson, and J. D. Groopman, “Aflatoxin M1 in human breast milk from the Gambia, West Africa, quantified by combined monoclonal antibody immunoaffinity chromatography and HPLC,” Carcinogenesis, vol. 13, no. 5, pp. 891–894, 1992.
[70]
M. J. Renfrew, A. M. W. Hay, N. Shelton et al., “Assessing levels of contaminants in breast milk: methodological issues and a framework for future research,” Paediatric and Perinatal Epidemiology, vol. 22, no. 1, pp. 72–86, 2008.
[71]
T. W. Kensler, B. D. Roebuck, G. N. Wogan, and J. D. Groopman, “Aflatoxin: a 50-year odyssey of mechanistic and translational toxicology,” Toxicological Sciences, vol. 120, supplement 1, pp. S28–S48, 2011.
[72]
V. M. Raney, T. M. Harris, and M. P. Stone, “DNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by aflatoxin B1 8,9-exo-epoxide,” Chemical Research in Toxicology, vol. 6, no. 1, pp. 64–68, 1993.
[73]
J. D. Groopman, A. J. Hall, H. Whittle et al., “Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in the Gambia, West Africa,” Cancer Epidemiology Biomarkers and Prevention, vol. 1, no. 3, pp. 221–227, 1992.
[74]
N. Polychronaki, C. P. Wild, H. Mykk?nen et al., “Urinary biomarkers of aflatoxin exposure in young children from Egypt and Guinea,” Food and Chemical Toxicology, vol. 46, no. 2, pp. 519–526, 2008.
[75]
J. Q. Zhu, L. S. Zhang, and X. Hu, “Correlation of dietary aflatoxin B1 levels with excretion of aflatoxin M1 in human urine,” Cancer Research, vol. 47, no. 7, pp. 1848–1852, 1987.
[76]
G. Sabbioni and C. P. Wild, “Identification of an aflatoxin G1-serum albumin adduct and its relevance to the measurement of human exposure to aflatoxins,” Carcinogenesis, vol. 12, no. 1, pp. 97–103, 1991.
[77]
B. D. Roebuck, W. G. Siegel, and G. N. Wogan, “In vitro metabolism of aflatoxin B2 by animal and human liver,” Cancer Research, vol. 38, no. 4, pp. 999–1002, 1978.
[78]
J. D. Groopman, K. W. Fowler, W. F. Busby Jr., and G. N. Wogan, “Interaction of aflatoxin B2 with rat liver DNA and histones in vivo,” Carcinogenesis, vol. 2, no. 12, pp. 1371–1373, 1981.
[79]
IARC, A Review of Human Carcinogens. Part F. Chemical Agents and Related Occupations, vol. 100, IARC, Lyon, France, 2012.
[80]
B. Chapot and C. P. Wild, “ELISA for quantification of aflatoxin-albumin adducts and their application to human exposure assessment,” in Techniques in Diagnostic Pathology, M. Warthol, D. van Velzer, and G. R. Bullock, Eds., vol. 2, pp. 135–155, Academic Press, London, UK, 1991.
[81]
L. F. McCoy, P. F. Scholl, R. L. Schleicher, J. D. Groopman, C. D. Powers, and C. M. Pfeiffer, “Analysis of aflatoxin B1-lysine adduct in serum using isotope-dilution liquid chromatography/tandem mass spectrometry,” Rapid Communications in Mass Spectrometry, vol. 19, no. 16, pp. 2203–2210, 2005.
[82]
P. F. Scholl, L. McCoy, T. W. Kensler, and J. D. Groopman, “Quantitative analysis and chronic dosimetry of the aflatoxin B1 plasma albumin adduct Lys-AFB1 in rats by isotope dilution mass spectrometry,” Chemical Research in Toxicology, vol. 19, no. 1, pp. 44–49, 2006.
[83]
P. F. Scholl, P. C. Turner, A. E. Sutcliffe et al., “Quantitative comparison of aflatoxin B1 serum albumin adducts in humans by isotope dilution mass spectrometry and ELISA,” Cancer Epidemiology Biomarkers and Prevention, vol. 15, no. 4, pp. 823–826, 2006.
[84]
R. L. Schleicher, L. F. McCoy, C. D. Powers, M. R. Sternberg, and C. M. Pfeiffer, “Serum concentrations of an aflatoxin-albumin adduct in the National Health and Nutrition Examination Survey (NHANES) 1999-2000,” Clinica Chimica Acta, vol. 423, pp. 46–50, 2013.
[85]
G. Sabbioni, P. L. Skipper, G. Buchi, and S. R. Tannenbaum, “Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1 in vivo in rats,” Carcinogenesis, vol. 8, no. 6, pp. 819–824, 1987.
[86]
G. Sabbioni, S. Ambs, G. N. Wogan, and J. D. Groopman, “The aflatoxin-lysine adduct quantified by high-performance liquid chromatography from human serum albumin samples,” Carcinogenesis, vol. 11, no. 11, pp. 2063–2066, 1990.
[87]
L. S. Gan, P. L. Skipper, X. Peng et al., “Serum albumin adducts in the molecular epidemiology of aflatoxin carcinogenesis: correlation with aflatoxin B1 intake and urinary excretion of aflatoxin M1,” Carcinogenesis, vol. 9, no. 7, pp. 1323–1325, 1988.
[88]
C. P. Wild, G. J. Hudson, G. Sabbioni et al., “Dietary intake of aflatoxins and the level of albumin-bound aflatoxin in peripheral blood in the Gambia, West Africa,” Cancer Epidemiology Biomarkers and Prevention, vol. 1, no. 3, pp. 229–234, 1992.
[89]
C. P. Wild, M. Fortuin, F. Donato et al., “Aflatoxin, liver enzymes, and hepatitis B virus infection in gambian children,” Cancer Epidemiology Biomarkers and Prevention, vol. 2, no. 6, pp. 555–561, 1993.
[90]
C. P. Wild, F. Yin, P. C. Turner et al., “Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia,” International Journal of Cancer, vol. 86, no. 1, pp. 1–7, 2000.
[91]
S. J. Allen, C. P. Wild, J. G. Wheeler et al., “Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 86, no. 4, pp. 426–430, 1992.
[92]
M. C. Hollstein, C. P. Wild, F. Bleicher et al., “p53 Mutations and aflatoxin B1 exposure in hepatocellular carcinoma patients from Thailand,” International Journal of Cancer, vol. 53, no. 1, pp. 51–55, 1993.
[93]
A. Hoque, Y. Z. Patt, B. Yoffe et al., “Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States?” Nutrition and Cancer, vol. 35, no. 1, pp. 27–33, 1999.
[94]
P. C. Turner, M. Mendy, H. Whittle, M. Fortuin, A. J. Hall, and C. P. Wild, “Hepatitis B infection and aflatoxin biomarker levels in Gambian children,” Tropical Medicine and International Health, vol. 5, no. 12, pp. 837–841, 2000.
[95]
P. C. Turner, S. E. Moore, A. J. Hall, A. M. Prentice, and C. P. Wild, “Modification of immune function through exposure to dietary aflatoxin in Gambian children,” Environmental Health Perspectives, vol. 111, no. 2, pp. 217–220, 2003.
[96]
P. C. Turner, A. Sylla, S. Y. Kuang et al., “Absence of TP53 codon 249 mutations in young Guinean children with high aflatoxin exposure,” Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 8, pp. 2053–2055, 2005.
[97]
P. C. Turner, A. Sylla, Y. Y. Gong et al., “Reduction in exposure to carcinogenic aflatoxins by postharvest intervention measures in west Africa: a community-based intervention study,” The Lancet, vol. 365, no. 9475, pp. 1950–1956, 2005.
[98]
P. C. Turner, A. C. Collinson, Y. B. Cheung et al., “Aflatoxin exposure in utero causes growth faltering in Gambian infants,” International Journal of Epidemiology, vol. 36, no. 5, pp. 1119–1125, 2007.
[99]
P. C. Turner, C. Loffredo, S. E. I. Kafrawy et al., “Pilot survey of aflatoxin-albumin adducts in sera from Egypt,” Food Additives and Contaminants A, vol. 25, no. 5, pp. 583–587, 2008.
[100]
P. C. Turner, J. A. Rothwell, K. L. M. White, Y. Gong, J. E. Cade, and C. P. Wild, “Urinary deoxynivalenol is correlated with cereal intake in individuals from the United kingdom,” Environmental Health Perspectives, vol. 116, no. 1, pp. 21–25, 2008.
[101]
P. C. Turner, V. J. Burley, J. A. Rothwell, K. L. M. White, J. E. Cade, and C. P. Wild, “Dietary wheat reduction decreases the level of urinary deoxynivalenol in UK adults,” Journal of Exposure Science and Environmental Epidemiology, vol. 18, no. 4, pp. 392–399, 2008.
[102]
Y. Y. Gong, K. Cardwell, A. Hounsa et al., “Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study,” British Medical Journal, vol. 325, no. 7354, pp. 20–21, 2002.
[103]
Y. Y. Gong, S. Egal, A. Hounsa et al., “Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning,” International Journal of Epidemiology, vol. 32, no. 4, pp. 556–562, 2003.
[104]
Y. Y. Gong, A. Hounsa, S. Egal et al., “Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa,” Environmental Health Perspectives, vol. 112, no. 13, pp. 1334–1338, 2004.
[105]
F. M. B. Shuaib, P. E. Jolly, J. E. Ehiri et al., “Association between birth outcomes and aflatoxin B1 biomarker blood levels in pregnant women in Kumasi, Ghana,” Tropical Medicine and International Health, vol. 15, no. 2, pp. 160–167, 2010.
[106]
H. Ahsan, L. Y. Wang, C. J. Chen, W. Y. Tsai, and R. M. Santella, “Variability in aflatoxin-albumin adduct levels and effects of hepatitis B and C virus infection and glutathione S-transferase M1 and T1 genotype,” Environmental Health Perspectives, vol. 109, no. 8, pp. 833–837, 2001.
[107]
M. S. Diallo, A. Sylla, K. Sidibe, B. S. Sylla, C. R. Trepo, and C. P. Wild, “Prevalence of exposure to aflatoxin and hepatitis B and C viruses in Guinea, West Africa,” Natural Toxins, vol. 3, no. 1, pp. 6–9, 1995.
[108]
C. J. Chen, M. W. Yu, Y. F. Liaw et al., “Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma,” The American Journal of Human Genetics, vol. 59, no. 1, pp. 128–134, 1996.
[109]
J. S. Wang, G. S. Qian, A. Zarba, et al., “Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People's Republic of China,” Cancer Epidemiology, Biomarkers and Prevention, vol. 5, pp. 253–261, 1996.
[110]
P. Wang, E. Afriyie-Gyawu, Y. Tang et al., “NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis. II: reduction in biomarkers of aflatoxin exposure in blood and urine,” Food Additives and Contaminants A, vol. 25, no. 5, pp. 622–634, 2008.
[111]
T. W. Kensler, X. He, M. Otieno et al., “Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers,” Cancer Epidemiology Biomarkers and Prevention, vol. 7, no. 2, pp. 127–134, 1998.
[112]
V. M. Scussel, P. Haas, Y. Y. Gong, P. C. Turner, and C. P. Wild, “Study of aflatoxin exposure in a Brazilian population using an aflatoxin-albumin biomarker,” in Mycotoxins and Phycotoxins: Advances in Determination, Toxicology and Exposure Management, H. Njapau, S. Trujillo, H. P. van Egmond, and D. L. Park, Eds., pp. 197–202, Wageningen Academic Publishers, Wageningen, The Netherlands, 2006.
[113]
B. C. Cupid, T. J. Lightfoot, D. Russell et al., “The formation of AFB1-macromolecular adducts in rats and humans at dietary levels of exposure,” Food and Chemical Toxicology, vol. 42, no. 4, pp. 559–569, 2004.
[114]
Y. Jiang, P. E. Jolly, W. O. Ellis, J. S. Wang, T. D. Phillips, and J. H. Williams, “Aflatoxin B1 albumin adduct levels and cellular immune status in Ghanaians,” International Immunology, vol. 17, no. 6, pp. 807–814, 2005.
[115]
Y. Jiang, P. E. Jolly, P. Preko et al., “Aflatoxin-related immune dysfunction in health and in human immunodeficiency virus disease,” Clinical and Developmental Immunology, vol. 2008, Article ID 790309, 12 pages, 2008.
[116]
M. Miele, F. Donato, A. J. Hall et al., “Aflatoxin exposure and cytogenetic alterations in individuals from the Gambia, West Africa,” Mutation Research, vol. 349, no. 2, pp. 209–217, 1996.
[117]
P. E. Jolly, F. M. Shuaib, Y. Jiang et al., “Association of high viral load and abnormal liver function with high aflatoxin B1-albumin adduct levels in HIV-positive Ghanaians: preliminary observations,” Food Additives and Contaminants A, vol. 28, no. 9, pp. 1224–1234, 2011.
[118]
Y. H. Leong, A. A. Latiff, N. I. Ahmad, and A. Rosma, “Exposure measurement of aflatoxins and aflatoxin metabolites in human body fluids. A short review,” Mycotoxin Research, vol. 28, no. 2, pp. 79–87, 2012.
[119]
C. P. Shirima, M. E. Kimanya, J. L. Kinabo et al., “Dietary exposure to aflatoxin and fumonisin among Tanzanian children as determined using biomarkers of exposure,” Molecular Nutrition and Food Research, vol. 57, no. 10, pp. 1874–1881, 2013.
[120]
E. E. Yard, J. H. Daniel, L. S. Lewis et al., “Human aflatoxin exposure in Kenya, 2007: a cross-sectional study,” Food Additives and Contaminants A, vol. 30, no. 7, pp. 1322–1331, 2013.
[121]
C. P. Wild, R. Hasegawa, L. Barraud et al., “Aflatoxin-albumin adducts: a basis for comparative carcinogenesis between animals and humans,” Cancer Epidemiology, Biomarkers and Prevention, vol. 5, no. 3, pp. 179–189, 1996.
[122]
C. P. Wild, F. N. Rasheed, M. F. B. Jawla, A. J. Hall, L. A. M. Jansen, and R. Montesano, “In-utero exposure to aflatoxin in West Africa,” The Lancet, vol. 337, no. 8757, p. 1602, 1991.
[123]
N. M. Johnson, G. Qian, L. Xu et al., “Aflatoxin and PAH exposure biomarkers in a U.S. population with a high incidence of hepatocellular carcinoma,” Science of the Total Environment, vol. 408, no. 23, pp. 6027–6031, 2010.
[124]
L. F. McCoy, P. F. Scholl, A. E. Sutcliffe et al., “Human aflatoxin albumin adducts quantitatively compared by ELISA, HPLC with fluorescence detection, and HPLC with isotope dilution mass spectrometry,” Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 7, pp. 1653–1657, 2008.
[125]
C. P. Wild, Y. Z. Jiang, S. J. Allen, L. A. M. Jansen, A. J. Hall, and R. Montesano, “Aflatoxin-albumin adducts in human sera from different regions of the world,” Carcinogenesis, vol. 11, no. 12, pp. 2271–2274, 1990.
[126]
D. I. Campbell, P. G. Lunn, and M. Elia, “Age-related association of small intestinal mucosal enteropathy with nutritional status in rural Gambian children,” British Journal of Nutrition, vol. 88, no. 5, pp. 499–505, 2002.
[127]
D. I. Campbell, M. Elia, and P. G. Lunn, “Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation,” Journal of Nutrition, vol. 133, no. 5, pp. 1332–1338, 2003.
[128]
D. I. Campbell, G. McPhail, P. G. Lunn, M. Elia, and D. J. Jeffries, “Intestinal inflammation measured by fecal neopterin in Gambian children with enteropathy: association with growth failure, Giardia lamblia, and intestinal permeability,” Journal of Pediatric Gastroenterology and Nutrition, vol. 39, no. 2, pp. 153–157, 2004.
[129]
P. G. Lunn, C. A. Northrop-Clewes, and R. M. Downes, “Intestinal permeability, mucosal injury, and growth faltering in Gambian infants,” The Lancet, vol. 338, no. 8772, pp. 907–910, 1991.
[130]
P. G. Lunn, “The impact of infection and nutrition on gut function and growth in childhood,” Proceedings of the Nutrition Society, vol. 59, no. 1, pp. 147–154, 2000.
[131]
A. Prentice, “Nutrient requirements for growth, pregnancy and lactation: the Keneba experience,” South African Journal of Clinical Nutrition, vol. 6, pp. 33–38, 1993.
[132]
S. E. Moore, A. C. Collinson, and A. M. Prentice, “Immune function in rural gambian children is not related to season of birth, birth size, or maternal supplementation status,” The American Journal of Clinical Nutrition, vol. 74, no. 6, pp. 840–847, 2001.
[133]
F. E. Jonsyn, S. M. Maxwell, and R. G. Hendrickse, “Human fetal exposure to ochratoxin A and aflatoxins,” Annals of Tropical Paediatrics, vol. 15, no. 1, pp. 3–9, 1995.
[134]
N. Sadeghi, M. R. Oveisi, B. Jannat, M. Hajimahmoodi, H. Bonyani, and F. Jannat, “Incidence of aflatoxin M1 in human breast milk in Tehran, Iran,” Food Control, vol. 20, no. 1, pp. 75–78, 2009.
[135]
S. M. Maxwell, J. B. Familusi, O. Sodeinde, M. C. K. Chan, and R. G. Hendrickse, “Detection of naphthols and aflatoxins in Nigerian cord blood,” Annals of Tropical Paediatrics, vol. 14, no. 1, pp. 3–5, 1994.
[136]
P. Khlangwiset, G. S. Shephard, and F. Wu, “Aflatoxins and growth impairment: a review,” Critical Reviews in Toxicology, vol. 41, no. 9, pp. 740–755, 2011.
[137]
S. Gratz, Q. K. Wu, H. El-Nezami, R. O. Juvonen, H. Mykk?nen, and P. C. Turner, “Lactobacillus rhamnosus strain GG reduces aflatoxin B1 transport, metabolism, and toxicity in Caco-2 cells,” Applied and Environmental Microbiology, vol. 73, no. 12, pp. 3958–3964, 2007.
[138]
Z. A. Bhutta, J. K. Das, A. Rizvi et al., “Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?” The Lancet, vol. 382, no. 9890, pp. 452–477, 2013.
[139]
R. E. Black, S. S. Morris, and J. Bryce, “Where and why are 10 million children dying every year?” The Lancet, vol. 361, no. 9376, pp. 2226–2234, 2003.
[140]
R. E. Black, C. G. Victora, S. P. Walker et al., “Maternal and child undernutrition and overweight in low-income and middle-income countries,” The Lancet, vol. 382, no. 9890, pp. 427–451, 2013.
[141]
A. D. Dangour, L. Watson, O. Cumming et al., “Interventions to improve water quality and supply, sanitation and hygiene practices, and their effects on the nutritional status of children,” Cochrane Database of Systematic Reviews, no. 8, Article ID CD009382, 2013.
[142]
J. Katz, A. C. Lee, N. Kozuki et al., “Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis,” The Lancet, vol. 382, no. 9890, pp. 417–425, 2013.
[143]
I. Olofin, C. M. McDonald, M. Ezzati et al., “Associations of suboptimal growth with all-cause and cause-specific mortality in children under five years: a pooled analysis of ten prospective studies,” PLoS ONE, vol. 8, no. 5, Article ID e64636, 2013.
[144]
N. G. Ilb?ck and G. Friman, “Interactions among infections, nutrients and xenobiotics,” Critical Reviews in Food Science and Nutrition, vol. 47, no. 5, pp. 499–519, 2007.
[145]
L. Y. Wang, M. Hatch, C. J. Chen et al., “Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan,” International Journal of Cancer, vol. 67, no. 5, pp. 620–625, 1996.
[146]
R. K. Ross, J. M. Yuan, M. C. Yu et al., “Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma,” The Lancet, vol. 339, no. 8799, pp. 943–946, 1992.
[147]
G. S. Qian, R. K. Ross, M. C. Yu et al., “A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People's Republic of China,” Cancer Epidemiology Biomarkers and Prevention, vol. 3, no. 1, pp. 3–10, 1994.
[148]
R. M. Lunn, Y. J. Zhang, L. Y. Wang et al., “p53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan,” Cancer Research, vol. 57, no. 16, pp. 3471–3477, 1997.
[149]
Z. Sun, P. Lu, M. H. Gail et al., “Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1,” Hepatology, vol. 30, no. 2, pp. 379–383, 1999.
[150]
G. S. Bondy and J. J. Pestka, “Immunomodulation by fungal toxins,” Journal of Toxicology and Environmental Health B, vol. 3, no. 2, pp. 109–143, 2000.
[151]
C. C. Barton, D. A. Hill, S. B. Yee, E. X. Barton, P. E. Ganey, and R. A. Roth, “Bacterial lipopolysaccharide exposure augments aflatoxin B1-induced liver injury,” Toxicological Sciences, vol. 55, no. 2, pp. 444–452, 2000.
[152]
J. P. Luyendyk, K. C. Shores, P. E. Ganey, and R. A. Roth, “Bacterial lipopolysaccharide exposure alters aflatoxin B1 hepatotoxicity: benchmark dose analysis for markers of liver injury,” Toxicological Sciences, vol. 68, no. 1, pp. 220–225, 2002.
[153]
J. P. Luyendyk, B. L. Copple, C. C. Barton, P. E. Ganey, and R. A. Roth, “Augmentation of aflatoxin B1 hepatotoxicity by endotoxin: involvement of endothelium and the coagulation system,” Toxicological Sciences, vol. 72, no. 1, pp. 171–181, 2003.
[154]
IRIN, “Study links hygiene and height,” 2013, http://www.irinnews.org/report/98504/study-links-hygiene-and-height.
[155]
BBC news online, “Clean water and soap ‘boost growth’ in young children,” 2013, http://www.bbc.co.uk/news/health-23519775.
[156]
J. D. Hayes, R. McLeod, E. M. Ellis et al., “Regulation of glutathione S-transferases and aldehyde reductase by chemoprotectors: studies of mechanisms responsible for inducible resistance to aflatoxin B1,” IARC Scientific Publications, no. 139, pp. 175–187, 1996.
[157]
B. D. Roebuck, Y. L. Liu, A. E. Rogers, J. D. Groopman, and T. W. Kensler, “Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry,” Cancer Research, vol. 51, no. 20, pp. 5501–5506, 1991.
[158]
Y. Li, J. J. Su, L. L. Qin et al., “Reduction of aflatoxin B1 adduct biomarkers by oltipraz in the tree shrew (Tupaia belangeri chinensis),” Cancer Letters, vol. 154, no. 1, pp. 79–83, 2000.
[159]
T. K. Bammler, D. H. Slone, and D. L. Eaton, “Effects of dietary oltipraz and ethoxyquin on aflatoxin B1 biotransformation in non-human primates,” Toxicological Sciences, vol. 54, no. 1, pp. 30–41, 2000.
[160]
M. G. Bolton, A. Munoz, L. P. Jacobson et al., “Transient intervention with oltipraz protects against aflatoxin-induced hepatic tumorigenesis,” Cancer Research, vol. 53, no. 15, pp. 3499–3504, 1993.
[161]
T. Primiano, P. A. Egner, T. R. Sutter, G. J. Kelloff, B. D. Roebuck, and T. W. Kensler, “Intermittent dosing with oltipraz: relationship between chemoprevention of aflatoxin-induced tumorigenesis and induction of glutathione S-transferases,” Cancer Research, vol. 55, no. 19, pp. 4319–4324, 1995.
[162]
T. W. Kensler, S. J. Gange, P. A. Egner et al., “Predictive value of molecular dosimetry: individual versus group effects of oltipraz on aflatoxin-albumin adducts and risk of liver cancer,” Cancer Epidemiology Biomarkers and Prevention, vol. 6, no. 8, pp. 603–610, 1997.
[163]
S. Langou?t, B. Coles, F. Morel et al., “Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture,” Cancer Research, vol. 55, no. 23, pp. 5574–5579, 1995.
[164]
P. Scholl, S. M. Musser, T. W. Kensler, and J. D. Groopman, “Inhibition of aflatoxin M1 excretion in rat urine during dietary intervention with oltipraz,” Carcinogenesis, vol. 17, no. 6, pp. 1385–1388, 1996.
[165]
B. C. Zhang, Y. R. Zhu, J. B. Wang et al., “Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China,” Journal of Cellular Biochemistry, vol. 28-29, pp. 166–173, 1997.
[166]
J. S. Wang, X. Shen, X. He et al., “Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 oltipraz in residents of Qidong, People's Republic of China,” Journal of the National Cancer Institute, vol. 91, no. 4, pp. 347–354, 1999.
[167]
J. W. Fahey and P. Talalay, “Antioxidant functions of sulforaphane: a potent inducer of phase II detoxication enzymes,” Food and Chemical Toxicology, vol. 37, no. 9-10, pp. 973–979, 1999.
[168]
T. W. Kensler, T. J. Curphey, Y. Maxiutenko, and B. D. Roebuck, “Chemoprotection by organosulfur inducers of phase 2 enzymes: dithiolethiones and dithiins,” Drug Metabolism and Drug Interactions, vol. 17, no. 1–4, pp. 3–22, 2000.
[169]
Z. Y. Wang, S. J. Cheng, Z. C. Zhou et al., “Antimutagenic activity of green tea polyphenols,” Mutation Research, vol. 223, no. 3, pp. 273–285, 1989.
[170]
L. Tang, M. Tang, L. Xu et al., “Modulation of aflatoxin biomarkers in human blood and urine by green tea polyphenols intervention,” Carcinogenesis, vol. 29, no. 2, pp. 411–417, 2008.
[171]
R. H. Dashwood, V. Breinholt, and G. S. Bailey, “Chemopreventive properties of chlorophyllin: inhibition of aflatoxin B1 (AFB1)—DNA binding in vivo and anti-mutagenic activity against AFB1 and two heterocyclic amines in the Salmonella mutagenicity assay,” Carcinogenesis, vol. 12, no. 5, pp. 939–942, 1991.
[172]
R. H. Dashwood, “The importance of using pure chemicals in (anti) mutagenicity studies: chlorophyllin as a case in point,” Mutation Research, vol. 381, no. 2, pp. 283–286, 1997.
[173]
P. A. Egner, J. B. Wang, Y. R. Zhu et al., “Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 25, pp. 14601–14606, 2001.
[174]
M. T. Simonich, P. A. Egner, B. D. Roebuck et al., “Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat,” Carcinogenesis, vol. 28, no. 6, pp. 1294–1302, 2007.
[175]
C. Jubert, J. Mata, G. Bench et al., “Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B1 pharmacokinetics in human volunteers,” Cancer Prevention Research, vol. 2, no. 12, pp. 1015–1022, 2009.
[176]
T. W. Kensler, P. A. Egner, J. B. Wang et al., “Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas,” Gastroenterology, vol. 127, no. 5, supplement 1, pp. S310–S318, 2004.
[177]
V. P. Kelly, E. M. Ellis, M. M. Manson et al., “Chemoprevention of aflatoxin B1 hepatocarcinogenesis by coumarin, a natural benzopyrone that is a potent inducer of aflatoxin B1-aldehyde reductase, the glutathione S-transferase A5 and P1 subunits, and NAD(P)H:quinone oxidoreductase in rat liver,” Cancer Research, vol. 60, no. 4, pp. 957–969, 2000.
[178]
C. Cavin, K. Mace, E. A. Offord, and B. Schilter, “Protective effects of coffee diterpenes against aflatoxin B1-induced genotoxicity: mechanisms in rat and human cells,” Food and Chemical Toxicology, vol. 39, no. 6, pp. 549–556, 2001.
[179]
E. O. Farombi, B. F. Adepoju, O. E. Ola-Davies, and G. O. Emerole, “Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural biflavonoid of Garcinia kola seeds,” European Journal of Cancer Prevention, vol. 14, no. 3, pp. 207–214, 2005.
[180]
M. S. Yates, M. K. Kwak, P. A. Egner et al., “Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1, 9(11)-dien-28-oyl]imidazole,” Cancer Research, vol. 66, no. 4, pp. 2488–2494, 2006.
[181]
T. D. Phillips, E. Afriyie-Gyawu, J. S. Wang, J. Williams, and H. Huebner, “The potential of aflatoxin sequestering clay,” in The Mycotoxin Fact Book, D. Barug, D. Bhatnagar, H. van Egmond, J. van der Kamp, W. van Osenbruggen, and A. Visconti, Eds., pp. 329–346, Wageningen Academic Publishers, Wageningen, The Netherlands, 2006.
[182]
E. Afriyie-Gyawu, J. Mackie, B. Dash et al., “Chronic toxicological evaluation of dietary NovaSil Clay in Sprague-Dawley rats,” Food Additives and Contaminants, vol. 22, no. 3, pp. 259–269, 2005.
[183]
J. S. Wang, H. Luo, M. Billam et al., “Short-term safety evaluation of processed calcium montmorillonite clay (NovaSil) in humans,” Food Additives and Contaminants, vol. 22, no. 3, pp. 270–279, 2005.
[184]
E. Afriyie-Gyawu, N. A. Ankrah, H. J. Huebner et al., “NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis. I. Study design and clinical outcomes,” Food Additives and Contaminants, vol. 25, no. 1, pp. 76–87, 2008.
[185]
N. J. Mitchell, J. Kumi, N. M. Johnson et al., “Reduction in the urinary aflatoxin M1 biomarker as an early indicator of the efficacy of dietary interventions to reduce exposure to aflatoxins,” Biomarkers, vol. 18, no. 5, pp. 391–398, 2013.
[186]
E. Azziz-Baumgartner, K. Lindblade, K. Gieseker et al., “Case-control study of an acute aflatoxicosis outbreak, Kenya,” Environmental Health Perspectives, vol. 113, no. 12, pp. 1779–1783, 2005.
[187]
L. Lewis, M. Onsongo, H. Njapau et al., “Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya,” Environmental Health Perspectives, vol. 113, no. 12, pp. 1763–1767, 2005.
[188]
Centers for Disease Control and Prevention (CDC), “Outbreak of aflatoxin poisoning—eastern and central provinces, Kenya,” Morbidity and Mortality Weekly Report, vol. 53, no. 34, pp. 790–793, 2004.
[189]
V. Breinholt, M. Schimerlik, R. Dashwood, and G. Bailey, “Mechanisms of chlorophyllin anticarcinogenesis against aflatoxin B1: complex formation with the carcinogen,” Chemical Research in Toxicology, vol. 8, no. 4, pp. 506–514, 1995.
[190]
V. Breinholt, J. Hendricks, C. Pereira, D. Arbogast, and G. Bailey, “Dietary chlorophyllin is a potent inhibitor of aflatoxin B1 hepatocarcinogenesis in rainbow trout,” Cancer Research, vol. 55, no. 1, pp. 57–62, 1995.
[191]
V. Breinholt, D. Arbogast, P. Loveland et al., “Chlorophyllin chemoprevention in trout initiated by aflatoxin B1 bath treatment: an evaluation of reduced bioavailability vs. Target organ protective mechanisms,” Toxicology and Applied Pharmacology, vol. 158, no. 2, pp. 141–151, 1999.
[192]
H. El-Nezami, P. Kankaanp??, S. Salminen, and J. Ahokas, “Physicochemical alterations enhance the ability of dairy strains of lactic acid bacteria to remove aflatoxin from contaminated media,” Journal of Food Protection, vol. 61, no. 4, pp. 466–468, 1998.
[193]
H. El-Nezami, P. Kankaanpaa, S. Salminen, and J. Ahokas, “Ability of dairy strains of lactic acid bacteria to bind a common food carcinogen, aflatoxin B1,” Food and Chemical Toxicology, vol. 36, no. 4, pp. 321–326, 1998.
[194]
H. El-Nezami, N. Polychronaki, S. Salminen, and H. Mykk?nen, “Binding rather than metabolism may explain the interaction of two food-grade Lactobacillus strains with zearalenone and its derivative ?-zearalenol,” Applied and Environmental Microbiology, vol. 68, no. 7, pp. 3545–3549, 2002.
[195]
I. Styriak and E. Conková, “Microbial binding and biodegradation of mycotoxins,” Veterinary and Human Toxicology, vol. 44, no. 6, pp. 358–361, 2002.
[196]
C. A. Haskard, H. S. El-Nezami, P. E. Kankaanp??, S. Salminen, and J. T. Ahokas, “Surface binding of aflatoxin B1 by lactic acid bacteria,” Applied and Environmental Microbiology, vol. 67, no. 7, pp. 3086–3091, 2001.
[197]
H. S. El-Nezami, A. Chrevatidis, S. Auriola, S. Salminen, and H. Mykk?nen, “Removal of common Fusarium toxins in vitro by strains of Lactobacillus and Propionibacterium,” Food Additives and Contaminants, vol. 19, no. 7, pp. 680–686, 2002.
[198]
H. Mykk?nen, H. Zhu, E. Salminen et al., “Fecal and urinary excretion of aflatoxin B1 metabolites (AFQ1, AFM1 and AFB-N7-guanine) in young Chinese males,” International Journal of Cancer, vol. 115, no. 6, pp. 879–884, 2005.
[199]
H. S. El-Nezami, N. N. Polychronaki, J. Ma et al., “Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China,” The American Journal of Clinical Nutrition, vol. 83, no. 5, pp. 1199–1203, 2006.
[200]
A. Hernandez-Mendoza, H. S. Garcia, and J. L. Steele, “Screening of Lactobacillus casei strains for their ability to bind aflatoxin B1,” Food and Chemical Toxicology, vol. 47, no. 6, pp. 1064–1068, 2009.
[201]
M. R. Fazeli, M. Hajimohammadali, A. Moshkani et al., “Aflatoxin B1 binding capacity of autochthonous strains of lactic acid bacteria,” Journal of Food Protection, vol. 72, no. 1, pp. 189–192, 2009.
[202]
A. Topcu, T. Bulat, R. Wishah, and I. H. BoyacI, “Detoxification of aflatoxin B1 and patulin by Enterococcus faecium strains,” International Journal of Food Microbiology, vol. 139, no. 3, pp. 202–205, 2010.
[203]
B. Kabak, E. F. A. Brandon, I. Var, M. Blokland, and A. J. A. M. Sips, “Effects of probiotic bacteria on the bioaccessibility of aflatoxin B1 and ochratoxin A using an in vitro digestion model under fed conditions,” Journal of Environmental Science and Health B, vol. 44, no. 5, pp. 472–480, 2009.
[204]
M. E. Kimanya, B. de Meulenaer, D. Roberfroid, C. Lachat, and P. Kolsteren, “Fumonisin exposure through maize in complementary foods is inversely associated with linear growth of infants in Tanzania,” Molecular Nutrition and Food Research, vol. 54, no. 11, pp. 1659–1667, 2010.
[205]
F. A. Meky, P. C. Turner, A. E. Ashcroft et al., “Development of a urinary biomarker of human exposure to deoxynivalenol,” Food and Chemical Toxicology, vol. 41, no. 2, pp. 265–273, 2003.
[206]
P. C. Turner, K. L. M. White, V. J. Burley et al., “A comparison of deoxynivalenol intake and urinary deoxynivalenol in UK adults,” Biomarkers, vol. 15, no. 6, pp. 553–562, 2010.
[207]
P. C. Turner, E. F. Taylor, K. L. M. White, J. E. Cade, and C. P. Wild, “A comparison of 24?h urinary deoxynivalenol with recent v. average cereal consumption for UK adults,” British Journal of Nutrition, vol. 102, no. 9, pp. 1276–1279, 2009.
[208]
S. J. Hepworth, L. J. Hardie, L. K. Fraser et al., “Deoxynivalenol exposure assessment in a cohort of pregnant women from Bradford, UK,” Food Additives and Contaminants A, vol. 29, no. 2, pp. 269–276, 2012.
[209]
L. van der Westhuizen, G. S. Shephard, J. P. Rheeder et al., “Simple intervention method to reduce fumonisin exposure in a subsistence maize-farming community in South Africa,” Food Additives and Contaminants A, vol. 27, no. 11, pp. 1582–1588, 2010.
[210]
L. Xu, Q. Cai, L. Tang et al., “Evaluation of fumonisin biomarkers in a cross-sectional study with two high-risk populations in China,” Food Additives and Contaminants A, vol. 27, no. 8, pp. 1161–1169, 2010.
[211]
R. T. Riley, O. Torres, J. L. Showker et al., “The kinetics of urinary fumonisin B1 excretion in humans consuming maize-based diets,” Molecular Nutrition and Food Research, vol. 56, no. 9, pp. 1445–1455, 2012.
[212]
B. Warth, M. Sulyok, P. Fruhmann, et al., “Development and validation of a rapid multi-biomarker liquid chromatography/tandem mass spectrometry method to assess human exposure to mycotoxins,” Rapid Communications in Mass Spectrometry, vol. 26, no. 13, pp. 1533–1540, 2012.
[213]
M. Solfrizzo, L. Gambacorta, V. M. T. Lattanzio, S. Powers, and A. Visconti, “Simultaneous LC-MS/MS determination of aflatoxin M1, ochratoxin A, deoxynivalenol, de-epoxydeoxynivalenol, α and β-zearalenols and fumonisin B1 in urine as a multi-biomarker method to assess exposure to mycotoxins,” Analytical and Bioanalytical Chemistry, vol. 401, no. 9, pp. 2831–2841, 2011.
[214]
W. A. Abia, B. Warth, M. Sulyok et al., “A mycotoxin co-exposure survey using human urine from Cameroon and a multi-biomarker approach,” Food and Chemical Toxicology, vol. 62, pp. 927–934, 2013.