赭曲霉毒素A
去异喹
细胞色素P450
苯巴比妥
药物代谢
致癌物
同工酶
生物化学
微粒体
内分泌学
赭曲霉毒素
生物
酶
内科学
化学
药理学
真菌毒素
CYP2D6型
生物技术
医学
作者
Eino Hietanen,H Bartsch,Béréziat Jc,M. Castegnaro,Jocelyne Michelon
出处
期刊:PubMed
日期:1991-01-01
卷期号: (115): 297-304
被引量:7
摘要
The phenotypic pattern of drug biotransformation is determined by both host and environmental factors. Debrisoquine is a good probe for phenotyping individuals, as its metabolism is not affected by age, gender, smoking habits or alcohol intake. People with Balkan endemic nephropathy or with urinary tract tumours in endemic areas are more frequently extensive metabolizers of debrisoquine than are healthy people. This finding has led to studies of the possible relationship between the metabolism of ochratoxin A and its toxicity and carcinogenicity on experimental models. Ochratoxin A is metabolized mainly in the liver into R- and S-isomers of 4- and 10-hydroxyochratoxin A, and the reaction is catalysed by cytochrome P450 haemoprotein. Animal species that are genetically different in their capacity to metabolize debrisoquine differ similarly in their capacity to metabolize ochratoxin A: female DA rats that are poor metabolizers of debrisoquine also poorly metabolize ochratoxin A, as assayed by urinary excretion of both the parent compound and of 4-hydroxyochratoxin A. Ochratoxin A hydroxylase activity is low in DA rat liver (and kidney) but is inducible by phenobarbital and 3-methylcholanthrene; debrisoquine hydroxylase is not known to be inducible by enzyme inducers. The reaction of ochratoxin A hydroxylase thus resembles those induced by 3-methyl-cholanthrene and catalysed by cytochrome P450IA. Ochratoxin A hydroxylase activity was further characterized in the livers of B6 and D2 mice that had been treated with typical enzyme inducers. Ochratoxin A hydroxylase was weakly inducible by phenobarbital, 3-methyl-cholanthrene and 2,4,7,8-tetrachlorodibenzodioxin.(ABSTRACT TRUNCATED AT 250 WORDS)
科研通智能强力驱动
Strongly Powered by AbleSci AI