Metabolism of a glucuronide conjugate of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats |
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Authors: | Sunday Ene-ojo Atawodi Kathrin Michelsen Elmar Richter |
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Institution: | 1. Walther Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians, Universit?t München, Nussbaumstrasse 26, D-80366, München, Germany
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Abstract: | Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-β-O-d-glucosiduronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
(NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke.
In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of 5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg 5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted
in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2±3.1% of the total radioactivity; the remaining part
of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6±1.7%) and its α-hydroxylation (11.5±2.2%)
and N-oxidation (3.6±1.6%) products. The presence of α-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite
may be activated in vivo to carcinogenic intermediates.
Received: 25 April 1994 / Accepted: 29 June 1994 |
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Keywords: | Tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone [4-(Methylnitrosamino)-1-(3-pyridyl)but-1-yl]- β -O-d-glucosiduronic acid Rat Urine Metabolism |
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