Metabolism and in vivo effects of cooked-food mutagens in the rat

Mutagenic and carcinogenic heterocyclic aromatic amines are formed in protein-rich food cooked under household conditions. The compounds have been shown to be activated mainly by cytochromes P-450IA1 and IA2. In the conventional rat, these P-450 enzymes were increased in the intestinal mucosa following oral administration of fried meat at a level comparable to human consumption. No such increase was observed in germfree rats. Furthermore, the metabolic disposition of the mutagenic material differed between the germfree and the conventional animals. A different urinary pattern of mutagenic metabolites and a substantially lower fecal mutagen excretion was observed in the germfree rats. The results implies a role of the intestinal microflora in the metabolism of fried meat mutagens.