Urinary O6-methylguanine excretion in the rat after O6-methylguanine but not N-methylnitrosourea administration.
Urinary makers that permit monitoring the exposure of rats to methylating carcinogens could be of considerable value. Because of the association of the formation and retention of O6-methylguanine (m6Gua) with carcinogenesis, the urinary recovery of this compound would be of particular interest. Urine of rats receiving 200 muCi 3H-methyl nitrosourea (MNU) was therefore subjected to HPLC analysis to detect labeled m6Gua. Following the intraperitoneal injection of 3H-MNU (16 or 80 mg/kg), 3H-m6Gua could not be detected in the urine, although its presence was demonstrated in liver DNA under such conditions. Rats were also administered 3H-MNU followed by pretreatment with unlabeled m6Gua to block the repair enzyme, m6G-DNA-transmethylase, which might have obscured an excision mechanism. This procedure permitted the recovery of about half of the administered dose of m6Gua in the urine, but none of this compound contained tritium. We conclude that m6Gua, though formed in the DNA from MNU, is not excised and excreted as such in the urine. Thus m6Gua could not be used to serve as a suitable urinary marker for exposure to methylating carcinogens.
Mandel
H G
HG
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Straw
J A
JA
Greene
P S
PS
Richardson
D C
DC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004247:DNA / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008715:Methionine / Q000378:metabolism; D008770:Methylnitrosourea / Q000378:metabolism* / Q000633:toxicity; D011687:Purines / Q000652:urine; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
D011687:Purines; D006147:Guanine; D008770:Methylnitrosourea; D004247:DNA; C008449:O-(6)-methylguanine; D008715:Methionine