EFFECTS OF GLYCOL ETHERS ON BONE MARROW PARAMETERS

乙二醇醚对骨髓参数的影响

• 批准号: 3918623
• 负责人: H L HONG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3918623
• 关键词: bone marrow; cytotoxicity; drug adverse effect; erythropoiesis; ethers; ethylene glycols; gender difference; histopathology; laboratory mouse; radiotracer; testis; toxin metabolism

Ethylene glycol (EG) or ethylene glycol monomethyl ether (EGMME) was administered by gavage to both sexes of B6C3F1 mice for 4 consecutive days at total doses of 200, 400, and 1000 mg/kg body weight. Bone marrow parameters were examined on days 1, 5, and 14 after there final treatment. Exposure to EG produced hypocellularity and suppression of granulocyte-macrophage progenitor (CFU-C) colony formation in both sexes on days 1 and 5 postexposure. Values returned to normal by dy 14 in the female mice but not in the males. Erythropoiesis, as measured by 59Fe incorporation and quantitation of erythroid precursors in culture (CFU-E), revealed no effect in female mice and affected male mice at the high dose only. In contrast, EGMME exposure in female mice resulted in inhibition of erythropoiesis. There was also a pronounced effect on white blood cells with decreased peripheral counts, and decreases in the number of CFU-C's cultured from marrow cells. The effect of EGMME has also seen at the lower dose levels and was sustained through the 14-day evaluation period. In addition, EGMME caused a 20% decrease in testicular weight, which was shown microscopically to be a segmented degeneration of seminiferous tubules, an effect not found with EG. This study demonstrates that EGMME is more myelotoxic in mice than EG and that pancytopenia is more pronounced in males, while erythropoiesis is more affected in females. These results were accepted for publication in J. Environ. Path. Toxicol. Oncol., 1988 (In press).

乙二醇（EG）或乙二醇单甲醚（EGMME） 通过管饲法向两种性别的B6 C3 F1小鼠施用4 以200、400和1000 mg/kg体重的总剂量连续给药 重量. 在第1、5和14天检查骨髓参数 最后一次治疗后。 接触产生的EG 细胞减少和粒细胞-巨噬细胞抑制 第1天和第5天两种性别的祖细胞（CFU-C）集落形成 实验后。 女性在第14天恢复正常 但在雄性中没有。 红细胞生成，通过59 Fe测量 培养物中红系前体的掺入和定量 （CFU-E），显示对雌性小鼠无影响，对雄性小鼠有影响 仅在高剂量下。 相比之下，雌性小鼠中的EGMME暴露 导致红细胞生成的抑制。 还有一 对白色血细胞有显著影响， 计数和骨髓CFU-C的数量减少 细胞 在较低剂量水平下也观察到EGMME的作用 并持续了14天的评估期。 在 此外，EGMME导致睾丸重量减少20%， 在显微镜下显示为节段性变性， 生精小管，EG未发现的效果。 本研究 表明EGMME在小鼠中比EG更具骨髓毒性， 全血细胞减少症在男性中更明显，而红细胞生成在男性中更明显。 在女性中更受影响。 这些结果被接受， 出版于J. Environ。病理学毒理学肿瘤，1988年（印刷中）。