Induction of aberrant crypt foci in C57BL/6N mice by 2-amino-9H-pyrido[2,3-b]indole (A alphaC) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx).

Abstract

The inductions of aberrant crypt foci (ACF) by two carcinogenic heterocyclic amines (HCAs), 2-amino-9H-pyrido[2,3-b]indole (A alphaC) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), were studied in the large intestine of C57BL/6N mice. Seven-week-old mice were fed a diet supplemented with 500 or 800 ppm of A alphaC, or 400 or 600 ppm of MeIQx for 7 weeks, followed by a basal diet for another 7 weeks. A alphaC at 800 ppm induced 8.0 +/- 1.9 and 7.8 +/- 2.5 ACF in female and male mice, respectively. MeIQx at 600 ppm induced 2.8 +/- 1.8 and 1.6 +/- 0.8 ACF in females and males, respectively. At lower concentrations of A alphaC and MeIQx, many fewer ACF were induced. No ACF were induced in the control group. The size of ACF (number of aberrant crypts/ACF) in all experimental groups was between 1.0 and 1.5. More than half the A alphaC-induced ACF were located in the region about 20-40% of the distance from the ileocecal portion to the anus. Although both of these HCAs were reported to induce tumors in the liver and other organs, but not in the large intestine, of CDF1 mice, these findings suggest that both these HCAs, and especially A alphaC, induce large intestinal tumors in C57BL/6N mice.