Enhanced repair of O6-alkylguanine in mammalian tissues.

Abstract

N-nitroso compounds and related alkylating agents react with several nucleophilic sites in DNA. One of the products, O6-alkylguanine, may be responsible for the carcinogenic effects of such agents as it can mispair with thymine during DNA replication, thereby affecting the integrity of the genome and consequently the repair of this lesion could be an important determinant in carcinogenesis. The use of both in vivo and in vitro procedures for the assay of the activity of this repair system have shown that it can be enhanced in rat liver by treatment with a variety of agents while in other species, the system is not only less effective but does not appear to respond to such treatments. Differences in the capacity and inducibility of this repair system may be related to the susceptibility of different species to tumour induction by chronic administration of nitrosamines.