Comparison in metabolic activity of cytochrome P450 1A1 on heterocyclic amines between human and rat.

摘要

In mutagenicity and antimutagenicity tests, the toxicants have been activated to the ultimate mutagenic forms usually with rat cytochrome P450 (CYP) enzymes. An understanding is important of whether these data can be available for human. In this paper are compared the activating abilities of CYP1A1 between human and rat using recombinant yeast cells that express respective CYP1A1 and yeast NADPH-CYP-oxidoreductase simultaneously. Three different types of dietary procarcinogens, heterocyclic amines, were tested by two methods: a bioassay with Salmonella mutagenicity test and a chemical determination of N-hydroxyls as the ultimate mutagenic forms. Compared with ED(50) values, saturation levels, and V(max)/K(m) values at an initial stage of the enzyme activity, human and rat CYP1A1 showed almost similar abilities for the metabolic activation on heterocyclic amines. The two enzymes also had the same preference for the tested procarcinogens and the same affinities to the specific inhibitors such as flavonoids.