INFLUENCE OF LONG-TERM ETHANOL TREATMENT ON RAT-LIVER BIOTRANSFORMATION ENZYMES
INFLUENCE OF LONG-TERM ETHANOL TREATMENT ON RAT-LIVER BIOTRANSFORMATION ENZYMES
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DOI：
10.1016/0741-8329(93)90027-l
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发表时间：
1993-09-01
期刊：
影响因子：
2.3
通讯作者：
BOS, RP
中科院分区：
文献类型：
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作者：
VANDEWIEL, JAG;FIJNEMAN, PHS;BOS, RP
研究了大鼠长期饮用乙醇对可能参与苯并（a）芘[B（a）P]生物转化的肝酶的影响。雄性和雌性Wistar大鼠在三周内在其饮用水中接受了增加量的乙醇至15%（w/v）。将乙醇含量保持在15%的浓度下另外三周。一组大鼠在乙醇处理的最后一周也接受了B（a）P。分离肝脏，并制备微粒体和胞质组分。在每种酶的测量中，观察到性别差异。长期饮用乙醇可诱导P450，尤其是苯胺4-羟化酶（P4502 E1）的表达。然而，雄性睾酮6 β-羟化酶（P4503 A2和P4502 Cl 3）和雌性睾酮12 β-羟化酶降低。2相酶谷胱甘肽S-转移酶（亚基1）和环氧化物水解酶的活性也降低。我们的研究结果支持了这一假设，即长期乙醇消费对B（a）P生物转化的影响，发现在体内和体外研究中，酚类和二醇类代谢产物的形成降低，是组成性P450同工酶减少的结果。
The influence of rats' long-term ethanol consumption on liver enzymes that could be involved in the biotransformation of benzo(a)pyrene [B(a)P] has been studied. Male and female Wistar rats received an increasing amount of ethanol in their drinking water up to 15% (w/v) in three weeks. The ethanol content was kept at a concentration of 15% for another three weeks. One group of rats also received B(a)P in the last week of the ethanol treatment. Livers were isolated, and microsomal and cytosolic fractions were prepared. In every enzyme measurement sex differences were observed. Long-term ethanol consumption induced P450, especially aniline 4-hydroxylase (P4502E1). However, testosterone 6beta-hydroxylase (P4503A2 and P4502Cl3) in males and testosterone 12beta-hydroxylase in females were decreased. The phase 2 enzymes glutathione S-transferase (subunit 1) and epoxide hydrolase were also decreased in their activity. Our results support the hypothesis that the effect of long-term ethanol consumption on B(a)P biotransformation as found in in vivo and in vitro studies, consisting of lowered formation of phenolic and diolic metabolites, is the result of a decrease of constitutive P450 isoenzymes.