Pruett S B, Barnes D B, Han Y C, Munson A E
Department of Biological Sciences, Mississippi State University, Mississippi State 39762.
Fundam Appl Toxicol. 1992 Jan;18(1):40-7. doi: 10.1016/0272-0590(92)90193-l.
This study was conducted to assess immunotoxicological effects and selected general toxicological effects of sodium methyldithiocarbamate (SMD). Initially, the compound was administered orally to female B6C3F1 mice at 300 mg/kg/day for 3, 5, 10, or 14 days. Body, liver, kidney, spleen, and thymus weights were measured. Selected hematological and bone marrow parameters were examined. Flow cytometric analysis was used to assess changes in lymphocyte subpopulations in the thymus and spleen, and production of antibody-forming cells in vitro was measured. Major effects included decreased thymus weight at all time points; increased spleen weight after 10 or 14 days of exposure, increased bone marrow cellularity after 10 or 14 days of exposure, significant decreases in mature lymphocyte subpopulations which were greater in the thymus than in the spleen, relatively selective depletion of the major subpopulation of thymocytes (CD4+CD8+), and decreased body weight. Overall patterns of changes were consistent with the conclusion that SMD rapidly depletes most CD4+CD8+ thymocytes, more slowly depletes a smaller number of mature lymphocytes in the thymus and spleen, and induces compensatory and/or detoxication mechanisms after 10-14 days of exposure. Subsequent experiments were done to assess selected immune function parameters. SMD at 50-300 mg/kg/day for 7 days caused substantial, dose-dependent suppression of NK cell activity. No suppression of antibody production in vivo or splenocyte responses to mitogens or allogeneic lymphocytes in vitro was detected. NK cell activity, thymus weight, and CD4+CD8+ thymocyte numbers were suppressed by dermal administration of SMD.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在评估甲基二硫代氨基甲酸钠(SMD)的免疫毒理学效应和选定的一般毒理学效应。最初,以300mg/kg/天的剂量对雌性B6C3F1小鼠进行为期3、5、10或14天的口服给药。测量了体重、肝脏、肾脏、脾脏和胸腺的重量。检查了选定的血液学和骨髓参数。采用流式细胞术分析评估胸腺和脾脏中淋巴细胞亚群的变化,并测量体外抗体形成细胞的产生。主要影响包括在所有时间点胸腺重量降低;暴露10或14天后脾脏重量增加,暴露10或14天后骨髓细胞增多,成熟淋巴细胞亚群显著减少,胸腺中的减少幅度大于脾脏,胸腺细胞主要亚群(CD4+CD8+)相对选择性耗竭,以及体重下降。总体变化模式与以下结论一致,即SMD迅速耗竭大多数CD4+CD8+胸腺细胞,更缓慢地耗竭胸腺和脾脏中数量较少的成熟淋巴细胞,并在暴露10 - 14天后诱导代偿和/或解毒机制。随后进行了实验以评估选定的免疫功能参数。以50 - 300mg/kg/天的剂量给予SMD 7天可导致NK细胞活性出现显著的剂量依赖性抑制。未检测到体内抗体产生受到抑制,也未检测到体外脾细胞对丝裂原或同种异体淋巴细胞的反应受到抑制。通过皮肤给药SMD可抑制NK细胞活性、胸腺重量和CD4+CD8+胸腺细胞数量。(摘要截断于250字)