Hepatic microsomal drug-metabolizing enzyme activity in non-human primates; the effect of repeated oral administration of DDT to baboons and rhesus monkeys

Abstract

1. Hepatic mocromosal N-demethylase activity was present in the order, rat > baboon > rhesus monkey. By contrast, O-demethylase activity was in the order, rhesus monkey > baboon > rat. Reductase and hydroxylase activities respectively were similar in each species. Chronic administration of DDT to each species caused increases (up to 2-fold) in these enzyme activities, in liver weight and in cytochrome P450 and protein concentrations. Glucuronyltransferase activity was present in the order, rhesus monkey > baboon > rat, and was lowered by DDT treatment. 2. Cytochrome P450 concentrations and O-demethylase activity in baboons were similar to that found in human, and similar to those found previously in baboons. 3. In the rat, increases in Phase I enzyme activities due to DDT treatment, appear to be compensated by increases in a detoxifying Phase II pathway, but this does not appear to be the case in non-human primates; thus the latter species could be more sensitive to toxic agents.