GENETIC DETERMINANT AND ENVIRONMENTAL CARCINOGENS

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abu ndant mutagenic heterocyclic amine (HCA) present in cooked foods. PhIP induces colon cancer in male Fischer 344 (F344) rats, and its role in human colon carcinogenesis has been suspected. To study the ecogeneti cs in PhIP colon carcinogenesis, rat system using aberrant crypt focus (ACF) formation as a phenotypic marker was applied. Among Buffalo (BU F), Brown Norway (BN), F344 and ACI/N (ACI) strains of rats, F344 rats produced a lower level of PhIP-DNA adducts than other three strains, and the number of ACFs/rat was highest in BUF, intermediate in BN and F344 and lowest in ACI. Thus there was no correlation between adduct l evels and number of ACF induced by PhIP. Fl progenies of BUF and ACI d eveloped ACF at a similar level to that of F344, and Fl progenies of F 344 and ACI developed ACF at a similar level to that of F344. Thus it was indicated that susceptibility of F344 to the ACF induction was aut osomally dominant over ACI rats. The results also suggest that BUF rat s have at least two genes, one is autosomally recessive against ACI ra ts and one is autosomally dominant similar to that F344 has. A total o f 170 progeny of ACI backcross of F344/ACI F-1 were examined for numbe r of ACFs and 65 progeny were phenotyped as F344 and 60 were ACI. Usin g these 125 rats, chromosomal mapping is being performed using markers of simple sequence length polymorphism (SSLP) and representational di fference analysis (RDA). By mapping the gene, we will be able to ident ify humans who might belong to high risk group in general population, and cancer can be prevented more efficiently by attaining early diagno sis. (C) 1998 Elsevier Science B.V. All rights reserved.