THE induction of tumours by dimethylnitrosamine and N-methyl-N-nitrosourea is thought to be initiated by the methylation of cellular constituents 1-3. Recent results have suggested that a critical product produced by these carcinogens and their ethyl analogues might be O6- alkylguanine in DNA2-5. Organs relatively resistant to the carcinogenic stimulus provided by these agents seem to have a greater ability to remove this alkylated purine from their DNA than more sensitive tissues 5-8. The activity of the system responsible for the removal of O 6-methylguanine from DNA may, therefore, play an important part in determining whether tumours are produced. The ability to remove O 6-methylguanine from DNA in rat kidney and liver showed a striking change in response to the dose of carcinogen administered. Large single doses of dimethylnitrosamine (20 mg per kg body weight or greater) which produce renal tumours in rats1,2 led to almost complete cessation of the excision of this product from kidney DNA8. In the rat liver removal of O 6-methylguanine still occurred after high doses of dimethylnitrosamine or N-methyl-N-nitrosourea but was much less efficient than after smaller doses9-11. All of the studies summarised above were carried out by following the persistence of labelled O6-alkylguanine in DNA in vivo following administration of radioactive N-nitroso-compounds. This report describes a comparison of the abilities of extracts derived from liver and kidneys of control rats and rats pretreated with dimethylnitrosamine to catalyse the loss of O6-methylguanine from acid-precipitable DNA in vitro.
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