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  • Title: Metabolism of 1,3-bis(2-chloroethyl)-1-nitrosourea by rat hepatic microsomes.
    Author: Lin HS, Weinkam RJ.
    Journal: J Med Chem; 1981 Jun; 24(6):761-3. PubMed ID: 7252986.
    Abstract:
    The in vitro metabolism of the anticancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been studied in male Fischer 344 rat liver microsomal preparations. The previously identified product. 1,3-bis(2-chloroethyl)urea (BCU), has been shown to be the major metabolite. Stable isotope labeling and mass spectral analysis of isolated metabolites indicate that BCU is formed exclusively from the metabolic denitrosation of BCNU. The rate of BCNU chemical decomposition in rat liver microsomal preparations deficient in NADPH and the metabolic disappearance rate in preparations containing added NADPH were measured and compared with the measured rate of metabolic formation of BCU under the same conditions. The rate of NADPH-dependent BCNU metabolism and BCU formation are equal within experimental error. BCNU was found to inhibit the rat liver 9000 g supernatant metabolism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
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