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Titolo:
INDUCTION OF CYTOCHROME-P450 2A6 EXPRESSION IN HUMANS BY THE CARCINOGENIC PARASITE INFECTION, OPISTHORCHIASIS-VIVERRINI
Autore:
SATARUG S; LANG MA; YONGVANIT P; SITHITHAWORN P; MAIRIANG E; MAIRIANG P; PELKONEN P; BARTSCH H; HASWELLELKINS MR;
Indirizzi:
KHON KAEN UNIV,FAC MED,DEPT BIOCHEM KHON KAEN 40000 THAILAND KHON KAEN UNIV,FAC MED,DEPT BIOCHEM KHON KAEN 40000 THAILAND KHON KAEN UNIV,FAC MED,DEPT PARASITOL KHON KAEN 40000 THAILAND KHON KAEN UNIV,FAC MED,DEPT RADIOL KHON KAEN 40000 THAILAND KHON KAEN UNIV,FAC MED,DEPT MED KHON KAEN 40000 THAILAND IARC,PROGRAM MOL TOXICOL F-69372 LYON FRANCE GERMAN CANC RES CTR,DIV TOXICOL & CANC RISK FACTORS D-69120 HEIDELBERG GERMANY NATL RES CTR ENVIRONM TOXICOL COPPERS PLAINS QLD 4108 AUSTRALIA
Titolo Testata:
Cancer epidemiology, biomarkers & prevention
fascicolo: 10, volume: 5, anno: 1996,
pagine: 795 - 800
SICI:
1055-9965(1996)5:10<795:IOC2EI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE; COUMARIN 7-HYDROXYLATION; NORTHEAST THAILAND; METABOLISM; LIVER; CHOLANGIOCARCINOMA; NITROSATION; NITROSAMINE; CANCER; VARIABILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
S. Satarug et al., "INDUCTION OF CYTOCHROME-P450 2A6 EXPRESSION IN HUMANS BY THE CARCINOGENIC PARASITE INFECTION, OPISTHORCHIASIS-VIVERRINI", Cancer epidemiology, biomarkers & prevention, 5(10), 1996, pp. 795-800

Abstract

The purpose of this study was to examine in vivo the activity of cytochrome P450 (CYP) 2A6, an enzyme capable of activating carcinogens, including N-nitrosodimethylamine, in humans with the carcinogenic liver fluke infection, opisthorchiasis viverrini, before and after treatmentwith the antiparasitic agent, praziquantel. Coumarin hydroxylase activity of CW 2A6 was assessed by administering a probe drug, coumarin, and measuring its metabolite, 7-hydroxycoumarin, in urines collected between 0-2 h and 2-4 h of 106 people with varying intensities of Opisthorchis viverrini infection, Five individuals who did not excrete any detectable 7-hydroxy coumarin (and have a genetic defect probably leading to an absence of catalytic activity of the CYP 2A6 protein) were excluded from analysis, Infected people excreted an average of 22.7 mu mol of 7-hydroxycoumarin in the first 2 h after taking the drug, whereas the mean of the uninfected group was 19.4 mu mol; this difference did not reach statistical significance (P = 0.10), However, a highly significant increase in CYP 2A6-related activity was observed in infectedindividuals who also had radiological evidence of biliary fibrosis (28.1 mu mol) compared to those without (19.4 mu mol; P = 0.01), Reassessments of coumarin hydroxylase activity of CYP 2A6 made 2 months afterpraziquantel treatment showed highly significant reductions in the amount of 7-hydroxycoumarin excreted among the infected groups but no difference in the uninfected group, These results suggest that expression of CW 2A6 is induced among chronically infected people who also havefibrosis of the intrahepatic bile duct, As already demonstrated in ananimal model and now observed in humans for the first time, this increase in CW 2A6-related enzyme activity may represent an important mechanistic link between inflammatory products of chronic liver fluke infection (e.g., DNA alkylation damage from endogenously formed N-nitrosamines) and the high risk of cholangiocarcinoma faced by infected individuals.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 11:00:28