The mutational spectra of carcinogenic heterocyclic
amines (HCAs), 2-amino-3,4-dimethylimidazo[4,5-b]
quinoline (
MeIQ), 2-amino-1-methyl-6-phenylimidazo[4,5-
b]pyridine (
PhIP) and 2-amino-9H-pyrido[2,3-b]
indole (A alphaC) were studied in the colon of Big Blue mice. In 90, 115 and 105 lacI mutants from mice fed 300 p.p.m.
MeIQ, 400 p.p.m.
PhIP and 800 p.p.m. A alphaC, respectively, 92, 115 and 105 mutations were identified. G:C-->T:A transversions predominated with these HCAs. Mutational hot spots for base-substitution mutations caused by
MeIQ,
PhIP and A alphaC were in distinct sequence contexts; at 5'-GC-3', in runs of
guanine and in 5'-CGT-3', respectively. Further, 30 of 115 (26%)
PhIP-induced mutations were G:C base pair deletions, and eight of these deletions were in 5'-GGGA-3'. The mutational characteristics of
MeIQ in the lacI gene coincided well with those in the Ha-ras gene of
MeIQ-induced mouse forestomach
tumors and rat Zymbal gland
tumors. The characteristic single-base deletion induced by
PhIP in the lacI gene also coincided well with those in the Apc gene of
PhIP-induced rat colon
tumors. These results suggest that the mutational characteristics of each chemical are conserved across different genes in different species.