Toxicity, mutation frequency and mutation spectrum induced by dacarbazine in CHO cells expressing different levels of O6-methylguanine-DNA methyltransferase

摘要: Abstract The toxicity and mutagenicity (including the mutation spectrum induced) of dacarbazine, a methylating cytostatic drug, was examined in CHO cells expressing different levels repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). Expression low or high transfected human MGMT gene under control metallothionein promoter protected against dacarbazine-induced mutagenesis. In absence expression, HPRT locus dominated by GC→AT transitions (mostly found at 5′Pu-G sequences), while there were also few AT→GC transitions. associated with substantial decrease mutations, suggesting that these mutations arose primarily via O6-methylguanine. These data illustrate important role latter lesion drug's mutagenic cytotoxic activity.