Hong H L, Boorman G A
Pathology Branch, National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1993 Nov;21(4):500-7. doi: 10.1006/faat.1993.1126.
Lindane (gamma-1,2,3,4,5,6-hexachlorocyclohexane), a widely used insecticide, may be found at low concentrations in the human diet. Male B6C3F1 mice given lindane daily at doses of 20 and 40 mg/kg body wt by gavage in corn oil for 3 days had suppressed bone marrow cellularity, erythrocyte precursors, granulocyte-macrophage progenitor cells (CFU-GM), and residual progenitor cell damage, which could be demonstrated by two whole-body irradiations (WBI) at 200 rads. Lindane exposure for 10 consecutive days at doses of 0, 10, or 20 mg/kg did not cause clinical abnormality or changes in body weights, but there were dose-dependent decreases in marrow cellularity, in more pluripotent stem cells and in committed CFU-GMs, which returned to control values by 4 weeks. These mice were then subjected to two 100-rad exposures of WBI at 4 and 9 weeks following cessation of lindane treatment. This level of irradiation caused only a transient drop in number of marrow progenitor cells. Control and lindane-exposed mice were examined at 1 and 6 weeks following the last irradiation, which was 10 and 15 weeks following the final lindane exposure. The lindane-exposed mice had lower progenitor cell numbers and slower recovery from the irradiation. These results indicate that lindane has significant myelotoxicity in mice and short-term lindane exposure can induce residual progenitor cell damage that can be demonstrated by subsequent irradiation.
林丹(γ-1,2,3,4,5,6-六氯环己烷)是一种广泛使用的杀虫剂,在人类饮食中可能以低浓度存在。通过玉米油灌胃,给雄性B6C3F1小鼠每日给予20和40毫克/千克体重的林丹,持续3天,其骨髓细胞数量、红细胞前体、粒细胞-巨噬细胞祖细胞(CFU-GM)受到抑制,且残留祖细胞损伤可通过两次200拉德的全身照射(WBI)得以证实。连续10天给予0、10或20毫克/千克剂量的林丹暴露,未导致临床异常或体重变化,但骨髓细胞数量、更多多能干细胞和定向CFU-GM出现剂量依赖性减少,4周后恢复至对照值。在停止林丹治疗后的第4周和第9周,对这些小鼠进行两次100拉德的WBI照射。这种照射水平仅导致骨髓祖细胞数量短暂下降。在最后一次照射后的第1周和第6周(即最后一次林丹暴露后的第10周和第15周)对对照小鼠和林丹暴露小鼠进行检查。林丹暴露小鼠的祖细胞数量较低,且从照射中恢复较慢。这些结果表明,林丹对小鼠具有显著的骨髓毒性,短期林丹暴露可诱导残留祖细胞损伤,后续照射可证实这一点。