Vaghef H, Wisén A C, Hellman B
Department of Occupational and Environmental Medicine, University Hospital, Uppsala, Sweden.
Pharmacol Toxicol. 1996 Jan;78(1):37-43. doi: 10.1111/j.1600-0773.1996.tb00177.x.
Alkaline single cell gel electrophoresis (also known as the 'comet assay') was used to measure DNA strand breaks and alkali-labile sites in peripheral lymphocytes, bone marrow and liver cells of C57BL/6 mice orally exposed to benzo(a)pyrene. Although this polycyclic aromatic hydrocarbon is a well-known genotoxic agent, little is known about to what extent it actually induces DNA strand breaks in peripheral lymphocytes and other tissues after in vivo exposure. Significant and dose-related damage was observed in liver cells after three days of exposure (lowest observed effect level being 3 x 100 mg benzo(a)pyrene/kg b.wt. No such damage could be observed in the lymphocytes and bone marrow cells even after administration of 3 x 150 mg benzo(a)pyrene/kg b.wt. The reference substance cyclophosphamide produced pronounced DNA damage in lymphocytes and bone marrow cells already in a single dose of 100 mg/kg b.wt. The present mouse study questions the usability of DNA strand breaks in peripheral lymphocytes as an indicator of benzo(a)pyrene-induced genotoxicity.
采用碱性单细胞凝胶电泳（也称为“彗星试验”）来检测经口暴露于苯并(a)芘的C57BL/6小鼠外周淋巴细胞、骨髓细胞和肝细胞中的DNA链断裂及碱不稳定位点。尽管这种多环芳烃是一种众所周知的遗传毒性剂，但对于其在体内暴露后实际诱导外周淋巴细胞和其他组织中DNA链断裂的程度知之甚少。暴露三天后，在肝细胞中观察到显著的剂量相关损伤（最低观察到效应水平为3×100mg苯并(a)芘/千克体重）。即使给予3×150mg苯并(a)芘/千克体重，在淋巴细胞和骨髓细胞中也未观察到此类损伤。参比物质环磷酰胺单剂量100mg/千克体重就已在淋巴细胞和骨髓细胞中产生明显的DNA损伤。本小鼠研究对将外周淋巴细胞中的DNA链断裂用作苯并(a)芘诱导遗传毒性指标的适用性提出了质疑。
