Evidence for 4-(3-pyridyl)-4-oxobutylation of DNA in F344 rats treated with the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine.
DNA was isolated from tissues of F344 rats 24 h after treatment by s.c. injection with [5-3H]4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ([5-3H]NNK) or [5-3H]N'-nitrosonornicotine ([5-3H]NNN). It was hydrolyzed with acid or at pH 7, 100 degrees C, and the hydrolysates were analyzed by HPLC. The major product in each case was identified as 4-hydroxy-1-(3-pyridyl)-1-butanone, formed by hydrolysis of a DNA adduct. It was detected in DNA from the livers of rats treated with [5-3H]NNK or [5-3H]NNN, and in DNA from lungs of rats treated with [5-3H]NNK. These results demonstrate that 4-(3-pyridyl)-4-oxobutylation of DNA occurs in rats treated with NNK or NNN, and are consistent with the hypothesis that these nitrosamines are metabolically activated by alpha-hydroxylation.
Hecht
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SS
Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, NY 10595.
Spratt
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TE
Trushin
N
N
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009602:Nitrosamines / Q000494:pharmacology*; D010947:Plants, Toxic; D051381:Rats; D011916:Rats, Inbred F344; D014026:Nicotiana
D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D004247:DNA; C008655:N'-nitrosonornicotine