Vaghef H, Hellman B
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Pharmacol Toxicol. 1998 Aug;83(2):69-74. doi: 10.1111/j.1600-0773.1998.tb01446.x.
Styrene (100-500 mg/kg b.wt.) and styrene oxide (50-200 mg/kg b.wt.) were given as a single intraperitoneal injection to female mice (C57BL/6) at various time intervals before sacrifice. Primary DNA damage in various organs was studied using alkaline single cell gel electrophoresis (comet) assay. Both substances induced significant DNA damage in lymphocytes, liver, bone marrow and kidney after 4 hr. The lymphocytes and liver cells were found to be the most sensitive cells to the DNA damaging effects of both agents. With the exception of bone marrow cells, the degree of DNA damage in all other cell types was decreased from 4 hr to 16 hr after the administration of both compounds. A strong sublinear dose-response relationship was observed in the lymphocytes, liver and bone marrow cells, possibly indicating a saturation of the detoxifying enzyme systems in these organs. The present work suggests that the comet assay can be used for detection of primary DNA damage induced by styrene and styrene oxide in vivo and for comparing the sensitivity of various target organs.
在处死前的不同时间间隔,给雌性C57BL/6小鼠腹腔注射一次苯乙烯(100 - 500毫克/千克体重)和环氧苯乙烷(50 - 200毫克/千克体重)。使用碱性单细胞凝胶电泳(彗星实验)研究各器官中的原发性DNA损伤。4小时后,两种物质均在淋巴细胞、肝脏、骨髓和肾脏中诱导了显著的DNA损伤。发现淋巴细胞和肝细胞对两种药剂的DNA损伤作用最为敏感。除骨髓细胞外,在给予两种化合物后4小时至16小时期间,所有其他细胞类型中的DNA损伤程度均降低。在淋巴细胞、肝脏和骨髓细胞中观察到强烈的亚线性剂量反应关系,这可能表明这些器官中的解毒酶系统饱和。本研究表明,彗星实验可用于检测体内苯乙烯和环氧苯乙烷诱导的原发性DNA损伤,并用于比较各种靶器官的敏感性。