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© 1989 Oxford University Press

research-article

Chromatographic detection of 7-methyladenine in urine of rats administered N-methylnitrosourea: a potential marker for monitoring exposure to methylating carcinogens

H.George Mandel 1 3, James A. Straw 1, Peter Farmer 2 and Janet Martin 2

1Department of Pharmacology, The George Washington University Medical Center Washington, DC 20037, USA
2MRC Toxicology Unit, Medical Research Council Laboratories Woodmansterne Road, Carshalton, Surrey SM5 4EF, UK

3To whom reprint request should be addressed

Relatively simple and rapid analytical procedures involving two sequential HPLC separations were developed for the isolation of methylated purines in the urine of rats administered radiolabeled methylating carcinogens. Following a dose of [3N-methyle-N-nitrosourea (MNU), 7-methyladenine (m7Ade) was detected by chromatography as a urinary methylpurine in addition to the expected 7-methylguanine (m7Gua) and 3-methylademne (m7 (m7 Ade). When methyl-labeled methionine was given to rats concurrently with MNU, urinary m7 Gua was labeled, but no radioactivity was recovered in either of the two methyladenine fractions. The profile of urinary methylated purines following a dose of dimethyl sulfate to the rat was similar. Small amounts of 1-methyladenine (m1 Ade) and 3-methylguanine (m7 Gua were also detected in the urine. The excretion of m3 Ade derived from the methyl group of the carcinogen rather than from the normal precursor for methylation, implies that this adduct, like m3 Ade may serve as an indicator in urine for exposure to methylating carcinogens.


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