AGREEMENT OF MUTATIONAL CHARACTERISTICS OF HETEROCYCLIC AMINES IN LACI OF THE BIG BLUE(R) MOUSE WITH THOSE IN TUMOR-RELATED GENES IN RODENTS

The mutational spectra of carcinogenic heterocyclic amines (HCAs), 2-a mino-3,4-dimethylimidazo[4,5-b]quinoline (MeIQ), 2-amino-1-methyl-6-ph enylimidazo[4,5-b]pyridine (PhIP) and 2-amino-9H-pyrido[2,3-b]indole ( A alpha C) were studied in the colon of Big Blue(R) mice, In 90, 115 a nd 105 lacI mutants from mice fed 300 p.p.m. MeIQ, 400 p.p.m. PhIP and 800 p.p.m. A alpha C, respectively, 92, 115 and 105 mutations were id entified, G:C-->T:A transversions predominated with these HCAs, Mutati onal hot spots for base-substitution mutations caused by MeIQ, PhIP an d A alpha C were in distinct sequence contexts; at 5'-GC-3', in runs o f guanine and in 5'-CGT-3', respectively, Further, 30 of 115 (26%) PhI P-induced mutations were G:C base pair deletions, and eight of these d eletions were in 5'-GGGA-3'. The mutational characteristics of MeIQ in the lad gene coincided well with those in the Ha-ras gene of MeIQ-ind uced mouse forestomach tumors and rat Zymbal gland tumors, The charact eristic single-base deletion induced by PhIP in the lad gene also coin cided well with those in the Ape gene of PhIP-induced rat colon tumors , These results suggest that the mutational characteristics of each ch emical are conserved across different genes in different species.