Main metabolites of 1-(2-chloroethyl)-3-(1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2',3', 4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea in rats
The metabolism of two glycosylnitrosoureas, 1-(2-chloroethyl)-3-(1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl)-1-nitrosourea (RFCNU) and 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea (RPCNU), has been investigated in the rat. With the label on the carboxyl moiety of RFCNU, we have shown that hydrolysis of the 4-nitrobenzoyl ester occurred to a large extent in vivo; 4-nitrobenzoic acid and its glucuronide were the major urinary metabolites. Two other minor metabolites and their glucuronides were identified as 4-aminobenzoic acid and 4-acetamidobenzoic acid. With the label on the chloroethyl moieties of RFCNU and RPCNU, we have shown that chloroethanol was a major degradation product of this alkylating part of the molecule. The concentration of chloroethanol in plasma vs. time has been determined. In urine, four metabolites derived from alkylated glutathione, namely thiodiacetic acid and its sulfoxide, N-acetylcarboxymethylcysteine, and N-acetylhydroxyethylcysteine, have been identified.
- Research Organization:
- INSERM U71, Faculte de Medecine, France
- OSTI ID:
- 6217575
- Journal Information:
- Drug Metab. Dispos.; (United States), Vol. 10:6
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
NITROSO COMPOUNDS
METABOLISM
METABOLITES
BIOLOGICAL PATHWAYS
BLOOD PLASMA
CARBON 14 COMPOUNDS
QUALITATIVE CHEMICAL ANALYSIS
RATS
TRACER TECHNIQUES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BODY FLUIDS
CHEMICAL ANALYSIS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RODENTS
VERTEBRATES
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560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques