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Titolo:
CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor
Autore:
Anttila, S; Tuominen, P; Hirvonen, A; Nurminen, M; Karjalainen, A; Hankinson, O; Elovaara, E;
Indirizzi:
Finnish Inst Occupat Hlth, FIN-00250 Helsinki, Finland Finnish Inst Occupat Hlth Helsinki Finland FIN-00250 0 Helsinki, Finland Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA Univ Calif Los Angeles Los Angeles CA USA & Lab Med, Los Angeles, CA USA Univ Calif Los Angeles, Johnson Comprehens Canc Ctr, Los Angeles, CA USA Univ Calif Los Angeles Los Angeles CA USA Canc Ctr, Los Angeles, CA USA
Titolo Testata:
PHARMACOGENETICS
fascicolo: 6, volume: 11, anno: 2001,
pagine: 501 - 509
SICI:
0960-314X(200108)11:6<501:CLILTO>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
CANCER SUSCEPTIBILITY; CYTOCHROME-P450IA1 GENE; HYDROXYLASE-ACTIVITY; MESSENGER-RNA; AH RECEPTOR; POPULATION; ASSOCIATION; MSPI; EXPRESSION; GENOTYPES;
Keywords:
CYP1A1; aromatic hydrocarbon receptor; induction; genetic polymorphism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Anttila, S Finnish Inst Occupat Hlth, Topeliuksenkatu 41 AA, FIN-00250 Helsinki, Finland Finnish Inst Occupat Hlth Topeliuksenkatu 41 AA Helsinki Finland FIN-00250
Citazione:
S. Anttila et al., "CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor", PHARMACOGEN, 11(6), 2001, pp. 501-509

Abstract

Induction of a polycyclic aromatic hydrocarbon-metabolizing cytochrome P450 isoform CYP1A1 is regulated by aromatic hydrocarbon receptor (AHR). High inducibility of CYP1A1, possibly due to genetic polymorphisms, has been considered to be a risk factor for lung cancer in tobacco smokers. The relationship between low or high pulmonary expression of CYP1A1 and polymorphic genotypes of CYP1A1 and AHR was investigated in 73 active smokers. CYP1A1 expression was determined in surgical lung samples by measuring ethoxyresorufin O-deethylase (EROD) activity and by immunostaining for CYP1A1 protein. The most common allelic variants of CYP1A1 and AHR in Finns, i.e. the MspI variant (CYP1A1*2A), 1462V variant (CYP1A1*2B), and -459C to T variant of CYP1A1 and the R554K variant (AHR*2) of AHR were studied using polymerase chain reaction based methods. EROD activity correlated positively with the daily cigarette consumption (r = 0.45). There was additional variation in EROD activity independent of the amount of smoking e.g. among those who smoked one pack per day until the day of operation, EROD activity ranged from 4-142(median 48) pmol/min/mg. The frequencies of the MspI, 462V, and -459T variant alleles of CYP1A1 and 554K variant allele of AHR were 0.158, 0.055, 0.055 and 0.075, respectively. No differences were observed in the frequenciesof polymorphic genotypes between the smokers with low and those with high expression, when the relationship was studied using a regression analysis adjusted for cigarette consumption. Our results thus indicate that the interindividual variation of CYP1A1 levels in smokers' lung tissue is not attributable to genetic polymorphisms of CYP1A1 or AHR tested in this study. Pharmacogenetics 11: 501-509 (C) 2001 Lippincott Williams & Wilkins.

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Documento generato il 31/03/20 alle ore 04:26:40