DNA adduct level induced by 2-amino-3,4-dimethylimidazo[4,5-f]-quinoline in Big Blue mice does not correlate with mutagenicity.
In previous experiments we analyzed the mutant frequency (MF) and mutational types in various organs of lacI transgenic mice which were fed a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food-borne mutagen/carcinogen. To clarify the relationships between mutational type and adduct molecular species and between adduct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was determined by the modified intensification method of 32P-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%. The difference in mutation type between bone marrow and other organs detected in the previous experiment was not explained by adduct molecular species. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in decreasing 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, lacI 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 detected in the heart, where no DNA replication is expected except for vascular 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.
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
M
M
Ochiai
K
K
Ishida
T
T
Ushijima
T
T
Suzuki
T
T
Sofuni
T
T
Sugimura
M
M
Nagao
D000818:Animals; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics*; D018736:DNA Adducts / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005260:Female; D056968:Lac Repressors; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D011804:Quinolines / Q000633:toxicity*; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution
D001426:Bacterial Proteins; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D009153:Mutagens; D011804:Quinolines; D012097:Repressor Proteins; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline