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Titolo:
Single nucleotide polymorphisms, metabolic activation and environmental carcinogenesis: why molecular epidemiologists should think about enzyme expression
Autore:
Williams, JA;
Indirizzi:
Inst Canc Res, Haddow Labs, Sutton SM2 5NG, Surrey, England Inst Canc ResSutton Surrey England SM2 5NG tton SM2 5NG, Surrey, England
Titolo Testata:
CARCINOGENESIS
fascicolo: 2, volume: 22, anno: 2001,
pagine: 209 - 214
SICI:
0143-3334(200102)22:2<209:SNPMAA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARYLAMINE N-ACETYLTRANSFERASE; MAMMARY EPITHELIAL-CELLS; LUNG-CANCER RISK; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN BREAST-TISSUE; HETEROCYCLIC AMINES; DNA-ADDUCTS; GENETIC POLYMORPHISMS; COOKED FOODS;
Tipo documento:
Editorial Material
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
89
Recensione:
Indirizzi per estratti:
Indirizzo: Williams, JA Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Dept Drug Disposit, Drop Code 0730, Indianapolis, IN 46285 USA Eli Lilly & Co Drop Code 0730 Indianapolis IN USA 46285 5 USA
Citazione:
J.A. Williams, "Single nucleotide polymorphisms, metabolic activation and environmental carcinogenesis: why molecular epidemiologists should think about enzyme expression", CARCINOGENE, 22(2), 2001, pp. 209-214

Abstract

This commentary was written to stimulate thoughts on, and consideration of, enzyme expression data in target organs when investigating possible associations between polymorphisms in carcinogen activation enzymes, lifestyle/dietary factors and cancer risk. The lung and breast are taken as examples. There is overwhelming evidence for a genotoxic mechanism in lung cancer development, and compelling evidence for the contribution of genotoxins to breast cancer aetiology, A consistent association has been shown where lung cancer risk is decreased by a G-->A polymorphism in the myeloperoxidase (MPO)gene, which is expressed in neutrophils recruited to the lung after chemical or immunological insults. In the breast, a consistent lack of association has been observed for women who are fast N-acetyltransferase type 2 (NAT2) acetylators consuming cooked meat. This could be explained by the lack ofdetectable NAT2-associated sulfamethazine acetylation activity in cytosolsprepared from mammary tissue, suggesting a minor contribution to carcinogen activation. The recent identification in mammary cytosols of detectable sulfotransferase isoforms (SULT1A1 and SULT1A3), which have high catalytic efficiency for activating N-hydroxylated heterocyclic amines (HCAs, mutagensin cooked meat), offers a more important role for these enzymes in the metabolic activation of genotoxins in the breast. The possible contribution ofMPO and lactoperoxidase enzymes to carcinogen activation in mammary tissueis also considered. Sulfotransferases and peroxidases have,vide substrate specificity in terms of carcinogen activation (HCAs, aromatic amines and polycyclic aromatic hydrocarbons-all present in cooked meat and tobacco smoke) compared with NATs (HCAs and aromatic amines only). For gene-environment interactions, investigations into functional polymorphisms in SULT and peroxidase genes may, therefore, offer new evidence for the involvement of genotoxins in the initiation of carcinogenesis. Identification of the isoforms (if any) of carcinogen activation enzymes that are expressed in the organs of interest will help to determine which genes to investigate in these studies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 17:30:34