Immunotoxicological Studies on thymocyte apoptosis and immunotoxicity which the organophosphorus insecticide induces

有机磷杀虫剂诱导胸腺细胞凋亡及免疫毒性的免疫毒理学研究

• 批准号: 08670409
• 负责人: KAWAMI Masaki
• 金额: $ 1.15万
• 依托单位: The Institute for Science of Labour
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670409/
• 关键词: chlorpyrifos; dichlofenthion; immunotoxicty; thymus atrophy; apoptosis; thymocytes subpopulation; organophosphorus insecticide; thymus microenvironment; ジクロフェンチオン; 動物実験

Chlorpyrifos (CP) and dichlofenthion (ECP) are widely used as organophosphorus insecticide. The purpose of this study is to examine the immunotoxicological effects of CP and ECP on the thymus of rat as target organ of immunotoxicty.The thymus of the F344 rat was studied in vitro and in vivo. For studies assessing the in vitro effect of si multaneous exposure of thymocytes to CP and ECP, rat thymocytes cultures were harvested and processed for flow cytometric analysis of DNA content. For the in vivo effect of CP and ECP, male F344 rats were exposed to CP (10, 20, 40mg/kg) and ECP (20, 40, 80mg/kg) by gavage, daily for 7 days.We observed that rat thymocytes cultures exposed to CP and ECP exhibited dose-dependent induction of apoptosis as a discrete subpopulation containing less than the diploid complement of DNA when analyzed by flow cytometry. On the in vivo effect of CP and ECP, we found that CP and ECP treatment induced significant thymic atrophy on highest dose. Determination of the thymocytes subpopulation showed a significant reduction of percentage of CD4+CD8+ cells as immature cells. Using a histochemical approach, on the thymus of ECP treatment. CD4+CD8+ cell in cortex were less frequently observed than vehicle control. The cortex of ECP-treated rat showed increased numbers of macrophages containing cell debris. These macrophages may correlate with subsequent removal of dead cell remnants by phagocytosis.These results suggest that CP and ECP induced thymus atrophy and reduction of percentage of CD4+CD8+ cells as immature cells, which might associate with apoptosis.

毒死蜱（CP）和敌敌畏（ECP）被广泛用作有机磷杀虫剂。本研究的目的是探讨CP和ECP对作为免疫毒性靶器官的大鼠胸腺的免疫毒理学作用。对F344大鼠的胸腺进行体外和体内研究。为了评估胸腺细胞同时暴露于 CP 和 ECP 的体外效果，收集并处理大鼠胸腺细胞培养物，用于 DNA 含量的流式细胞术分析。对于 CP 和 ECP 的体内作用，将雄性 F344 大鼠通过管饲法暴露于 CP（10、20、40mg/kg）和 ECP（20、40、80mg/kg），持续 7 天。我们观察到暴露于 CP 和 ECP 的大鼠胸腺细胞培养物作为含有少于二倍体补体的离散亚群表现出剂量依赖性凋亡诱导。 通过流式细胞术分析时的 DNA 。关于 CP 和 ECP 的体内作用，我们发现 CP 和 ECP 治疗在最高剂量时会诱导显着的胸腺萎缩。胸腺细胞亚群的测定显示未成熟细胞的 CD4+CD8+ 细胞百分比显着降低。采用组织化学方法，对胸腺进行ECP治疗。皮层中 CD4+CD8+ 细胞的观察频率低于载体对照。 ECP处理的大鼠皮层显示含有细胞碎片的巨噬细胞数量增加。这些巨噬细胞可能与随后通过吞噬作用清除死细胞残余物有关。这些结果表明，CP 和 ECP 诱导胸腺萎缩和 CD4+CD8+ 细胞作为未成熟细胞的百分比减少，这可能与细胞凋亡有关。

项目成果

Masaki Kawami, Isamu Ebihara: "Studies on thymic atrophy of in vivo treated with organophosphorus pesticides"J Occup Health. 40. 463 (1998)

Masaki Kawami、Isamu Ebihara：“有机磷农药处理体内胸腺萎缩的研究”J Occup Health。

川見 正機,海老原 勇他: "有機リン系殺虫剤投与にともなう胸腺萎縮発現と胸腺微小環境" 日本農村医学会雑誌. 47(3). 279 (1998)

Masaki Kawami、Isamu Ebihara 等人：“与施用有机磷杀虫剂相关的胸腺萎缩和胸腺微环境”，日本农村医学学会杂志 47(3) 279 (1998)。

川見 正機, 海老原 勇: "有機リン系殺虫剤投与にともなう胸腺萎縮発現と胸腺微小環境"日本農村医学会雑誌. 47(3). 279 (1998)

Masaki Kawami、Isamu Ebihara：“与施用有机磷杀虫剂相关的胸腺萎缩和胸腺微环境”，日本农村医学学会杂志 47(3) (1998)。

川見 正機, 海老原 勇: "有機リン系殺虫剤投与にともなう胸腺萎縮発現に関する研究"産業衛生学雑誌. 40. 463 (1998)

Masaki Kawami、Isamu Ebihara：“与施用有机磷杀虫剂相关的胸腺萎缩的表现的研究”工业卫生杂志 40. 463 (1998)。

Masaki Kawami, Isamu Ebihara: "Thymic atrophy expression and thymus micro environment with the organophosphorus insecticide administration"J Japanese Assoc Rural Med. 47(3). 279 (1998)

Masaki Kawami、Isamu Ebihara：“施用有机磷杀虫剂时的胸腺萎缩表现和胸腺微环境”J Japanese Assoc Rural Med。