In vitro single-strand DNA damage and cancer cell cytotoxicity effects of Temozolomide

Temozolomide (TMZ) is approved against certain tumors, but substantial evidences are scarce to demonstrate TMZ as single-strand DNA break agent and reasons behind lack of responses in carcinoma. Plasmid and genomic DNA included as a substrate during assessment of in vitro single-strand break potential of TMZ. Cell based assay was performed to assess DNA damaging activity and cytotoxicity in HeLa. Further, authors tried to evaluate DNA damage and overall cytotoxicity in HeLa using Trypan blue dye exclusion and apoptotic DNA fragmentation assays. Data indicate that TMZ can generate extensive single-strand break on different DNA substrate. A DNA ligase inhibitor L189 appears to plays synergistic role in TMZ ability to decrease cell proliferation in HeLa and some extent of cytotoxicity. However, authors noticed none apoptotic DNA fragments due to toxicity effects of TMZ alone or combined TMZ plus L189. Based on our observations, findings support combined use of TMZ and L189 inhibitor to enhance responsiveness in HeLa possibly by decreasing cellular growth instead of apoptotic cell death pathway.