Ž . Mutation Research 395 1997 93–99 Effects of gender and species on spectra of mutation induced by w x 2-amino-1-methyl-6-phenylimidazo 4,5-b pyridine in the lacI transgene Hideo Okonogi a , Gregory R. Stuart b , Eriko Okochi a , Toshikazu Ushijima a , Takashi Sugimura a , Barry W. Glickman b , Minako Nagao a, ) a Carcinogenesis DiÕision, National Cancer Center Research Institute, 1-1, Tsukiji 5, Chuo-ku, Tokyo 104, Japan b Centre for EnÕironmental Health, Department of Biology, UniÕersity of Victoria, P.O. Box 3020, Victoria, B.C., Canada V8W 3N5 Received 30 June 1997; revised 4 August 1997; accepted 4 August 1997 Abstract w x Ž . Feeding of 2-amino-1-methyl-6-phenylimidazo 4,5-b pyridine PhIP to F344 rats induces colon tumors specifically in male rats. Mutant frequencies and mutational spectra of the lacI transgene were studied in male and female Big Blue w transgenic rats after feeding 400 ppm of PhIP in the diet for 60 days. Mutant frequencies in the colon mucosa were increased 20–25 times compared with those of the control rats, being 661.4 "33.3 =10 y6 and 718.2 "16.9 =10 y6 in males and females, respectively. No significant differences in types and distribution of the mutations were detected between males and females. One-base deletions were the most frequent mutation, including the characteristic guanine deletion at 5 X -GGGA-3 X which is also seen in the Apc gene of rat colon cancers induced by PhIP. Comparison of the lacI mutations in the rat colon with those previously identified in the mouse colon showed that the rate of G to T transversions was significantly higher in the mouse. This is the first report stating that there exist differences in the mutation specificity on the same gene, among mammalian species. However, the characteristic guanine deletion was recovered in both the mouse and the rat. These findings do not offer a mechanistic explanation of the gender specificity of PhIP-induced colon cancer in rats, though the universality of the guanine deletion suggests that this alteration may prove a useful indicator of human exposure. q 1997 Elsevier Science B.V. w x Keywords: 2-Amino-1-methyl-6-phenylimidazo 4,5-b pyridine; lacI gene; Mutation, spectrum, frequency; Gender effect; Species specificity 1. Introduction w x 2-Amino-1-methyl-6-phenylimidazo 4,5-b pyri- Ž . dine PhIP is a food borne carcinogen to which humans are exposed on daily basis. PhIP induces ) Corresponding author. colon and prostate cancers in male Fischer 344 rats w x 6,13 and mammary cancer, but not colon cancer, in wx female rats 6 . However, similar levels of PhIP-DNA adducts are produced in the colon of male and w x female rats exposed to PhIP in the diet 11 . DNA adduct formation is not a sole factor for induction of a mutation which is an important process of carcino- wx genesis 1 . Mutation frequencies are the result of combination of the level of DNA adducts and the 1383-5718r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S1383-5718 97 00146-0