Chromatographic detection of 7-methyladenine in urine of rats administered N-methylnitrosourea: a potential marker for monitoring exposure to methylating carcinogens.
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 [3H]N-methyl-N-nitrosourea (MNU), 7-methyl-adenine (m7Gua) was detected by chromatography as a urinary methylpurine in addition to the expected 7-methylguanine (m7Gua) and 3-methyladenine (m3Ade). When methyl-labeled methionine was given to rats concurrently with MNU, urinary m7Gua 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 (m1Ade) and 3-methylguanine (m3Gua) were also detected in the urine. The excretion of m7Ade derived from the methyl group of the carcinogen rather than from the normal precursor for methylation, implies that this adduct, like m3Ade, may serve as an indicator in urine for exposure to methylating carcinogens.
Mandel
H G
HG
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Straw
J A
JA
Farmer
P B
PB
Martin
J
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D008715:Methionine / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology*; D013463:Sulfuric Acid Esters / Q000494:pharmacology
D013463:Sulfuric Acid Esters; C008407:1-methyladenine; C025946:3-methyladenine; D008770:Methylnitrosourea; C059225:7-methyladenine; D008715:Methionine; D000225:Adenine; C007482:dimethyl sulfate