DNA ADDUCT LEVEL INDUCED BY 2-AMINO-3,4-DIMETHYLIMIDAZO[4,5-F]QUINOLINE IN BIG BLUE(TM) MICE DOES NOT CORRELATE WITH MUTAGENICITY

In previous experiments we analyzed the mutant frequency (MF) and muta tional types in various organs of lad transgenic mice which were fed;a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinolin e (MeIQ), a food-borne mutagen/carcinogen, To clarify the relationship s between mutational type and adduct molecular species and between add uct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was det ermined by the modified intensification mel.hod of P-32-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N-2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%, The d ifference in mutation type between bone marrow and other organs detect ed in the previous experiment was not explained by adduct molecular sp ecies. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in de creasing order, with values of 28,3, 8,4, 3,3, 1.3 and 0.4 molecule/10 (7) nucleotides at 12 weeks. Based on our previously reported data, la d MF was highest in the colon and those in the liver, bone marrow and forestomach were 10-60% of that of the colon; no increase in MF was de tected in the heart, where no DNA replication is expected except for v ascular endothelial cells, There was no direct relationship between MF and adduct level. The MF may be the product of adduct level and cell proliferation rate.