O6-Alkylguanine DNA alkyltransferase activity in monkey, human and rat liver

Abstract

Previous studies have shown that in in vitro assays using methylated DNA substrates, human and rat liver fractions were able to catalyse the repair of the promutagenic lesion O⁶-methylguanine (O⁶-meG). These studies have been extended to include monkey liver fractions and the repair of O⁶-ethylguanine (O⁶-etG). Human and monkey liver fractions have similar capacities for the repair of O⁶-meG and are 8 – 10 times more active than rat liver fractions. In all species examined, the liver extracts showed a lower capacity to repair O⁶-etG and the rate of repair was dependent on the degree of modification of the DNA substrate and the protein concentration used. The in vitro metabolism of dimethylnitrosamine (DMN), an alkylating carcinogen, by liver slices, has been previously demonstrated in these three species, but the activity in monkey liver was considerably lower compared with human and rat liver. The lack of evidence of a carcinogenic effect of DMN in the monkey liver could be correlated to this low capacity to metabolise DMN and the high O⁶-alkyl-guanine-DNA alkyltransferase levels in this organ.