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This volume represents the proceedings of a NATO Advanced Study
Institute on "Molecular Aspects of Monooxygenases and Bioactivation
of Toxic Compounds" which was held in ~e me (Izmir) Turkey, August
27 to September 7, 1989. The Institute emphasized the potential
dangers of drugs, pollutants, pesticides, carcinogens, and both
nutrient and non-nutrient food additives and their interactions at
the molecular level. These xenobiotics are metabolized in phase I
reactions by monooxygenases, primarly cytochrome P450-isozyme
dependent, followed by phase II conjugation enzymes. The
versatility of these enzymes is unique in biochemistry since they
catalyze the metabolism of an almost limitless number of compounds
through a diverse array of reactions. Although these metabolic
sequences are usually detoxication mechanisms, in some cases the
reactive intermediates are more mutagenic, more carcinogenic and
ultimately more toxic than the parent compound. The Institute was
devoted to recent scientific progress in the understanding of the
biochemical and molecular properties of these enzymes and factors
that influence the metabolism of chemicals to toxic and non-toxic
compounds. Overview lectures focused on xenobiotic metabolism by
cytochrome P450, the flavin-containing monooxygenase, cytochrome
b5, epoxide hydrolase, glutathione S-transferase and
UDP-glucuronosyl transferase. Several additional presentations
stressed various aspects of cytochrome P450 mediated metabolism
including: specific forms in the rabbit and insects; topology in
membranes; posttranslational modification; control of constitutive
forms in the rat; hormonal and xenobiotic regulation; prostanoid
metabolism; endogenous substrate metabolism; interaction with
estrogenic pesticides; pesticide bioactivation. The Institute also
included talks on interactions between enzymes and on benzene
metabolism and toxicity.
Presented here are recent advances in biochemical, toxicological,
and regulatory aspects of oxidative drug metabolizing enzymes.
Mainly cytochrome P450-dependent and flavin-containing
monooxygenases (FMO) are covered. Moreover, the book deals with
genotoxicity studies and toxicological interactions of
environmental chemicals and mechanisms of mutagenicity and tumor
formation. The construction of genetically engineered mammalian
cells for the production of a specific P450 isozyme and the
application of these cell lines in drug metabolism, mutagenicity
and toxicity studies are described in detail. Further, insight is
provided into how a number of aquatic species cope with pollutants
and their genotoxicity.
The NATO Advanced Study Institute of "Molecular and Applied Aspects
of Oxida- tive Drug Metabolizing Enzymes" was held in Tekirova,
Antalya, Turkey, from August 31 to September 11, 1997. This
Institute was the third of a series of the NATO ASIs on a similar
topic relating to the enzymes of oxidative metabolism of
xenobiotics. The first NATO ASI in this series, entitled "Molecular
Aspects of Monooxygenases and Bioactiva- tion of Toxic Compounds"
(NATO ASI Series A: Life Sciences, Vol. 202), was held in
The NATO Advanced Study Institute of "Molecular and Applied Aspects
of Oxida- tive Drug Metabolizing Enzymes" was held in Tekirova,
Antalya, Turkey, from August 31 to September 11, 1997. This
Institute was the third of a series of the NATO ASIs on a similar
topic relating to the enzymes of oxidative metabolism of
xenobiotics. The first NATO ASI in this series, entitled "Molecular
Aspects of Monooxygenases and Bioactiva- tion of Toxic Compounds"
(NATO ASI Series A: Life Sciences, Vol. 202), was held in
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