Sabourin P J, Bechtold W E, Birnbaum L S, Lucier G, Henderson R F
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Toxicol Appl Pharmacol. 1988 Jun 15;94(1):128-40. doi: 10.1016/0041-008x(88)90343-2.
Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene, were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity.
苯是一种强效血液毒素，已被证明可导致人类患白血病。慢性毒性研究表明，B6C3F1小鼠比F334/N大鼠对苯毒性更敏感。本文所呈现研究的目的是确定F344/N大鼠和B6C3F1小鼠之间是否存在代谢差异，这可能是导致这种易感性增加的原因。在暴露于50 ppm苯蒸气6小时期间及之后，对血液、肝脏、肺和骨髓中的苯代谢物进行了测量。反映导致苯潜在毒性代谢物形成途径的对苯二酚葡萄糖醛酸苷、对苯二酚和粘康酸，在小鼠组织中的浓度比在大鼠组织中高得多。解毒代谢物苯硫酸酯和一种未知的水溶性代谢物在这两个物种中的浓度大致相等。这些结果表明，与解毒途径相比，B6C3F1小鼠中通过导致潜在毒性代谢物形成的途径代谢的苯比例比F344大鼠高得多，这可能解释了小鼠对苯诱导的血液毒性和致癌性更高的易感性。
