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Titolo:
Genetic susceptibility to adverse effects of drugs and environmental toxicants - The role of the CYP family of enzymes
Autore:
Ingelman-Sundberg, M;
Indirizzi:
Karolinska Inst, Div Mol Toxicol, Inst Environm Med, IMM, S-17177 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17177 IMM, S-17177 Stockholm, Sweden
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 482, anno: 2001,
pagine: 11 - 19
SICI:
1386-1964(20011001)482:1-2<11:GSTAEO>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
NICOTINE METABOLISM; POLYMORPHISMS; DUPLICATION; RISK; DEBRISOQUINE; SMOKING; CYP2D6-ASTERISK-10; IDENTIFICATION; METAANALYSIS; ASSOCIATION;
Keywords:
genetic polymorphism; ultra-rapid metabolism; poor metabolisers; drug adducts; genotyping; idiosyncratic drug toxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Ingelman-Sundberg, M Karolinska Inst, Div Mol Toxicol, Inst Environm Med, IMM, Box 210, S-17177Stockholm, Sweden Karolinska Inst Box 210 Stockholm Sweden S-17177 den
Citazione:
M. Ingelman-Sundberg, "Genetic susceptibility to adverse effects of drugs and environmental toxicants - The role of the CYP family of enzymes", MUT RES-F M, 482(1-2), 2001, pp. 11-19

Abstract

The majority of cytochrome P450 (CYP)-dependent xenobiotic metabolism is carried out by polymorphic and inducible enzymes which can cause abolished, quantitatively or qualitatively altered or enhanced drug metabolism. Stableduplication, multi-duplication or amplification of active genes, most likely in response to dietary components causing a selection of alleles with multiple genes, has been described. Several examples exist where subjects carrying certain alleles suffer from a lack of drug efficacy due to ultra-rapid metabolism caused by multiple genes or by induction of gene expression or, alternatively, adverse effects from the drug treatment due to the presence of defective alleles. The polymorphism of CYP enzymes is expected to influence the individual sensitivity and toxicity for different environmental agents, although there is no real consensus in the literature about specificfirm relationships in this regard. Dosage requirements for several commonly used drugs that have a narrow therapeutic range can differ more than 20-fold dependent on the genotype or the enzyme expression status. The incidence of serious and fatal adverse drug reactions has been found to be very high among hospitalised patients and causes over 100 000 deaths per year in the US, making it between the 4th and 6th leading cause of death, It is likely that predictive genotyping could avoid 10-20% of these deaths. In the present contribution, an overview is presented about our present knowledge about the polymorphism of xenobiotic metabolising CYPs and the importance for adverse effects of drugs and metabolic activation of xenobiotics. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 22:19:17