反复口服苯暴露会改变参与苯代谢的酶。

D. Daiker, M. T. Moslen, J. Carr, J. Ward
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引用次数: 9

摘要

苯是人类和实验动物中已知的致癌物和造血毒素。急性高剂量苯暴露对肝脏生物活化和解毒酶的影响已经确定,而反复低剂量苯暴露对这些酶的影响知之甚少。我们的目的是确定反复的口服苯暴露是否会改变参与苯代谢的酶。具体来说,我们关注细胞色素P-450-2E1,一种生物活化酶,以及谷胱甘肽转移酶和醛脱氢酶,两种解毒酶。雌性CD-1小鼠分别以5 mg/kg (0.064 mmol/kg)或50 mg/kg (0.646 mmol/kg)玉米油苯灌胃3周。这些剂量的苯分别产生0.048和0.236个muconic酸/d。我们发现,在不影响醛脱氢酶活性的情况下,反复暴露于50 mg /kg/d的苯使P-450-2E1活性降低34%,诱导谷胱甘肽转移酶活性降低30%。这些酶活性的变化可能起到防止反复接触苯的保护作用。
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Repeated oral benzene exposure alters enzymes involved in benzene metabolism.
Benzene is a known carcinogen and hematopoietic toxin in humans and experimental animals. The effect of acute, high-dose exposure to benzene on hepatic bioactivation and detoxication enzymes has been defined, while little is known about the effect of repeated, low-dose benzene exposure on these enzymes. Our objective was to determine whether repeated, oral benzene exposure alters enzymes involved in benzene metabolism. Specifically, we were concerned with cytochrome P-450-2E1, a bioactivation enzyme, and glutathione transferase and aldehyde dehydrogenase, two detoxifying enzymes. Female CD-1 mice were treated by gavage for 3 wk with benzene doses of 5 mg/kg (0.064 mmol/kg) or 50 mg/kg (0.646 mmol/kg) in corn oil. These doses of benzene produced 0.048 and 0.236 mumol muconic acid/d, respectively. We found that repeated exposure to 50 mg benzene/kg/d decreased P-450-2E1 activity by 34% and induced glutathione transferase activity by 30% without affecting aldehyde dehydrogenase activity. These changes in enzyme activities may serve a protective role against repeated exposure to benzene.
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