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Read e-book online Biological Basis of Detoxication PDF

By John Caldwell

ISBN-10: 0121550605

ISBN-13: 9780121550608

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Studies on hepatic microsomal N-dealkylation reaction. Molecular oxygen as the source of the oxygen atom. J. Am. Chem. Soc. 91, 3389-3390. 20. McMahon, R. , Sullivan, H. , Craig, J. C , and Pereirea, W. E. (1969). The microsomal oxygenation of ethyl benzene: Isotopic, stereochemical, and induction studies. Arch. Biochem. Biophys. 132, 575-577. 21. Klingenberg, M. (1958). Pigments of rat liver microsomes. Arch. Biochem. Biophys. 75, 376-386. 22. Garfinkel, D. (1958). Studies on pig liver microsomes.

Carcinogen activation is further partitioned in the competition between DNA modification and the combined effects of glutathione Stransferase-mediated detoxication and hydrolysis. These are quantita­ tively determined by G, the glutathione detoxication factor. G = kmA[ONA]/(kmo + kGSH) (3) Glutathione conjugation is assumed to be the only reaction other than hydrolysis that is quantitatively significant in removal of ultimate electrophiles. Enzymatic and nonenzymatic reactions of GSH are included in kGSH.

1), have been purified from both rat and rabbit liver microsomes. 43,44 Indeed, the purification of eight distinct forms of cytochrome P-450 from uninduced rabbit liver microsomes has been reported. 45 The relative concentrations of these forms can be dramatically altered by exposure in vivo to inducers such as phenobarbital, stilbene oxide, pregnenolone 16-carbonitrile, ethanol, isosafrole, and poly cyclic aromatic compounds that also increase total cytochrome P-450 levels. For many of these inducers, one or two distinct forms predominate that may be difficult even to detect in uninduced microsomes.

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