Heterocyclic aromatic amine-DNA-adducts in bacteria and mammalian cells detected by 32P-postlabeling analysis

Abstract
The formation of DNA adducts by the fried meat mutagen and carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied by means of 32P-postlabeling of DNA digests and four-directional t.l.c. Three major and five minor adducts were detected in assays of DNA digest obtained from Salmonella typhimurium TA98 cells after treatment with IQ and rat liver postmitochondrial supernatant (S9). A qualitatively identical adduct pattern was obtained with nitroIQ (3-methyl-2-nitroimidazo[4,5-f]quinoline), a new analogue of IQ with a nitro instead of the amino group. These two compounds, therefore, form the same ultimate metabolite. The same adduct pattern was also found after TA98/1,8-DNP6 (acetyltransferase-deficient) cells were treated with nitro-IQ; this is probably due to a residual acetyltransferase activity in this strain. Upon treatment of TA98 cells with 1 mM IQ for 3 h one adduct was detected in 4.7 .times. 105 total bases; a considerably higher adduct frequency, one in 4.2 .times. 103, was induced by nitro-IQ (70 .mu.M, 30 min). The IQ isomer 2-amino-1-methylimidazo[4,5-f]quinoline (isoIQ) and its nitroanalogue nitro-isoIQ (1-methyl-2-nitroimidazo[4,5-f]-quinoline) also produced identical adducts. Their common adduct pattern was very similar to the IQ adduct pattern but was located in a position different from that of the IQ adduct pattern. DNA from Syrian hamster embryo (SHE) cells treated with IQ and S9 exhibited adducts apparently identical with those of Salmonella DNA.

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