Pretreatment with acetylaminofluorene enhances the repair of O6-methylguanine in DNA.

Abstract

Epidemiological and experimental evidence suggests that the interplay of environmental factors may be particularly relevant to the induction of cancer in man. We have investigated the possible interrelationships, at the level of DNA repair, of two chemically different hepatocarcinogens administered to rats. Animals were pretreated for several weeks by inclusion of 2-acetylaminofluorene (AAF) in the diet and a study was made of the capacity of liver to repair lesions subsequently introduced into DNA by a pulse of dimethylnitrosamine (DMN). Of particular interest was the repair of adducts at the O6 position of guanine as this product has been implicated as a critical reaction site for carcinogenesis by the monofunctional alkylating agents. We show here that the capacity of liver to repair O6-methylguanine in DNA is enhanced by prolonged exposure of rats to the chemically unrelated agent, AAF.