DNA was isolated from tissues of K344 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'-nitrosonor-nicotine ([5-3H]NNN) It was hydrolyzed with acid or at pH 7,100°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 α-hydroxylation.
Bibliographical noteFunding Information:
This study was supported by grant no. 44377 from the National Cancer Institute. This is paper no. 113 in 'A Study of Chemical Carcinogenesis'.