The ability of human and rabbit gastrointestinal-tract microsomes to metabolize the heterocyclic amine 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline (MeIQ) to a mutagen was determined with the Ames test. When human jejunal and ileal microsomes were used as the metabolic activation source, MeIQ produced 1675 and 388 revertants/mg of microsomal protein, respectively, and this increased to 29,230 and 17,963 revertants/mg of microsomal protein, respectively, in the presence of 100 µm α-naphthoflavone. MeIQ in the presence of control rabbit duodenal, jejunal, and ileal microsomes produced 2304 ± 1018, 988 ± 386, and 444 ± 134 (mean ± SD, four samples) revertants/mg of microsomal protein, respectively. In the presence of α-naphthoflavone (100 µm), these activities increased >7-fold. P4503A proteins were detectable on Western blots of microsomes prepared from both human and rabbit small intestine. Further, rifampicin-induced rabbit hepatic-microsomal activation of MeIQ was completely inhibited at low concentrations of α-naphthoflavone, but at higher concentrations (i.e., 100 µm) this returned to control levels. Flavone also caused a marked stimulation of MeIQ activation in human and rabbit gastrointestinal-tract microsomes. The aforementioned data suggest that flavonoids markedly increase the ability of P4503A isozymes to activate heterocyclic amines to mutagens in the Ames test.
Presented at “Nutrition and Cancer,” the first conference of the International Conference Series on Nutrition and Health Promotion, April 17–19, 1991, Atlanta, GA. This work was supported by grants from the Australian National Health and Medical Research Council and the Anti-Cancer Foundation of the Universities of South Australia.