Abstract
Five heterocyclic aromatic amines (HAAs) formed during the cooking of proteinaceous foods, were found to be genotoxic in an in vitro assay for unscheduled DNA synthesis (UDS), in rat and hamster hepatocytes. A larger UDS response was induced in hamster hepatocytes than rat cells, probably due to the greater activation capabilities of the hamster hepatocytes. Low levels of UDS were induced by HAAs in vivo, with a greater response observed in rats than hamsters. Rats also showed their peak UDS response after longer exposure periods than hamsters. MelQ (2-amino-3,4-dimethylimidazo[4,5-f]-quinoline) elicited the greatest UDS response, both in vitro and in vivo, and this response was comparable with that of the carcinogen 2-acetylaminofluorene (AAF). The host-mediated assay (HMA), which measured the induction of revertants of Salmonella typhimurium TA98 in the livers of mice, was a more sensitive in vivo assay for the genotoxicity of the HAAs. MelQ, which showed the most potent response, and 3-amino-l-methyl-5H-pyrido(4,3-b)-indole (Trp-P-2) exhibited different pharmacokinetics in the HMA. The in vivo genotoxicity of MelQ, Trp-P-2 and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the HMAs was significantly reduced by feeding mice diets containing fibre such as wheat bran, corn bran, lignin and cabbage. Distribution studies using [14C]-MeIQ showed that less was present in the livers of mice on a 30% bran diet, than in livers of mice fed a fibre-free diet, at the timepoints studied. In mice fed the fibre-free diet, [14C]-MeIQ was rapidly absorbed from the small intestine and widely distributed throughout the body in organs such as the liver, kidneys, lungs and spleen. In bran-fed mice, gastric emptying and absorption from the small intestine was delayed, and less [14C]-MeIQ was present in the liver, spleen, kidneys and lungs. This may be due to MelQ binding to the wheat bran in the mouse gastrointestinal tract.