We have recently shown that immunodeficient (SCID) mice, which lack functional T and B cells, are highly susceptible to low dose site specific induction of colon
aberrant crypt foci (ACF), surrogates for colon
tumors, by 2-amino-3-methylimidazo[4,5-f ]
quinoline (IQ). To test whether long-term exposure to a high dose in the diet might prove carcinogenic to the SCID mouse colon, in contrast to other mice strains tested to date, the compound was administered at 300 p.p.m. in the diet to female 6-7-week-old SCID mice for 32 weeks. IQ induced high numbers of ACF, hyperplastic
polyps, dysplasia, and colon
adenomas, as well as hepatocellular altered foci and liver
adenomas. Induction of colon
tumors did not correlate with the main sites where ACF developed, the proximal colon, however, being seen mainly in the mid and distal colon. Induction of colon
tumors correlated significantly with the incidence of dysplasia, crypt height, the mitotic index, cell proliferation and numbers of
8-hydroxydeoxyguanosine (8-OHdG)-positive cells in the colon crypt, particularly in mid and distal colon. Administration of 20% omega-6
polyunsaturated fatty acids (
corn oil), omega-3
polyunsaturated fatty acids (
perilla oil), or
monounsaturated fatty acids (
olive oil) simultaneously with IQ in the diet resulted in: (i) inhibition of colon and liver
tumor induction by corn and
perilla oil, whereas
olive oil showed no effects; (ii) no reduction in total numbers of ACF by
corn oil or
perilla oil but significant suppression in the
olive oil treated group; (iii) inhibition of
tumor development particularly by omega-3
polyunsaturated fatty acids in
perilla oil, correlating significantly with decreased cell proliferation in both colon and liver and a marked decrease in crypt heights and mitotic indices. Selective reduction in the numbers of 8-OHdG-positive nuclei, mainly in the middle and distal colon crypts, was also found to correlate with
tumor inhibition. Thus, the results indicate carcinogenicity of IQ in the colon of the SCID mouse and preventive effects of
polyunsaturated fatty acids.