2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine induction of recombinational mutations in mammalian cell lines as detected by DNA fingerprinting

Abstract

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant mutagenic heterocyclic amine in cooked foods. Two mouse tumor cell lines, BMT11 and FM3A, were exposed to its proximate form, 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP). Fifty-six subclones of BMT11 and 39 subclones of FM3A were isolated and analyzed by DNA fingerprinting. Treatment with 10-20 microM N-OH-PhIP gave rise to extra bands or shifted bands, but treatment without N-OH-PhIP did not. This suggests that mutations resulting from recombination were induced. The mutation frequencies were 21-53% and 22-35% for BMT11 and FM3A, respectively. These findings suggest that PhIP induces recombinational mutations.