Mutagenesis vol.17 no.6 pp.483–487, 2002 Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine

Alkylating agents are a structurally diverse group of com-pounds that cause a wide range of biological effects, including cell death, mutation and cancer. DNA damaged by these agents contains widely different amounts of 12 alkylated purines/pyrimidines and two phosphotriester isomers. The biological effects appear to be mediated predominantly by attack at the O6 position of guanine. DNA extracted from various normal human tissues contains detectable levels of O6-alkylguanine, the source of which has not been defined. Given that, following DNA replication, this lesion cannot only generate point mutations but can also initiate mismatch repair-mediated DNA recombination and cell death, it seems worthwhile to consider the possible contribution of these events and cell killing to the aetiology of human cancer. There is increasing evidence that poin