Carlson G P
School of Health Sciences, Purdue University, West Lafayette, Indiana 47907-1338, USA.
J Toxicol Environ Health. 1997 Jun 6;51(2):177-87. doi: 10.1080/00984109708984020.
Styrene is known to cause both hepatotoxicity and pneumotoxicity in mice. Strain differences have been reported by other investigators suggesting that Swiss mice are less susceptible than non-Swiss mice to styrene-induced liver damage. In this study, A/J and C57BL/6 mice were found to be similar to non-Swiss albino (NSA) mice in susceptibility whereas CD-1 (Swiss) mice were more resistant to hepatotoxicity as assessed by serum sorbitol dehydrogenase levels and pneumotoxicity as determined by gamma-glutamyltranspeptidase and lactate dehydrogenase measurements in bronchoalveolar lavage fluid. Styrene was hepatotoxic in CD-1 mice treated with pyridine to induce CYP2E1. CYP2E1 apoprotein levels and p-nitrophenol hydroxylase activities in control and pyridine-induced mice were similar in the two strains. Hepatic and pulmonary microsomal preparations from both strains metabolized styrene to styrene oxide at similar rates. CD-1 mice were as susceptible as the NSA mice to the effects of styrene oxide. The data suggest that there are no differences in the bioactivation of styrene to styrene oxide or innate susceptibility to the active metabolite that would account for the differences between the CD-1 and NSA mice.
已知苯乙烯会在小鼠中引起肝毒性和肺毒性。其他研究人员报告了品系差异，表明瑞士小鼠比非瑞士小鼠对苯乙烯诱导的肝损伤更不易感。在本研究中，发现A/J和C57BL/6小鼠在易感性方面与非瑞士白化病（NSA）小鼠相似，而CD-1（瑞士）小鼠对肝毒性更具抗性，这通过血清山梨醇脱氢酶水平评估，对肺毒性更具抗性，这通过支气管肺泡灌洗液中的γ-谷氨酰转肽酶和乳酸脱氢酶测量来确定。在用吡啶诱导CYP2E1的CD-1小鼠中，苯乙烯具有肝毒性。在两个品系中，对照小鼠和吡啶诱导小鼠的CYP2E1载脂蛋白水平和对硝基苯酚羟化酶活性相似。两个品系的肝和肺微粒体制剂将苯乙烯代谢为环氧苯乙烯的速率相似。CD-1小鼠对环氧苯乙烯的作用与NSA小鼠一样敏感。数据表明，在苯乙烯生物活化生成环氧苯乙烯或对活性代谢物的固有易感性方面没有差异，这可以解释CD-1小鼠和NSA小鼠之间的差异。
