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Methylated Purines in Human Liver DNA after Probable Dimethylnitrosamine Poisoning¹

Departments of Community and Environmental Medicine [R. C. S.] and Medical Pharmacology and Therapeutics [D. C. H.], University of California, Irvine, California 92717

DNA, isolated from two samples of human liver obtained from a suspected dimethylnitrosamine poisoning, contained 1363 to 1373 µmol of 7-methylguanine per mol of guanine and 273 to 317 µmol of O⁶-methylguanine per mol of guanine. Liver and kidney DNA obtained from unrelated cases contained no detectable methylated purines. From the DNA methylation levels, it is estimated that the dimethylnitrosamine-poisoning victim had been exposed to a dose of 20 mg or more of dimethylnitrosamine per kg of body weight. The results indicate for the first time that humans, like rodents, appear to activate dimethylnitrosamine metabolically to a strong methylating agent, resulting in methylation of liver DNA at both the 7- and O⁶ positions of guanine.

¹ This work was supported by the Environmental Toxicology Laboratories, College of Medicine, University of California, Irvine, Calif.

² To whom requests for reprints should be addressed.

Received 1/ 7/80. Accepted 5/19/80.

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