EVALUATION OF CHEMICAL MYELOTOXICITY USING AN IN VIVO LEUKEMIA TRANSPLANT MODEL

在NTP 2中使用的高达30%的Fischer 344/N品系大鼠- 一年毒性和致癌性研究自发发展 白血病开始于大约18个月，这降低了 检测化学性白血病的敏感性。An In 体内细胞移植模型被开发用于转移白血病 脾细胞从自发性白血病大鼠转化为幼鼠， 健康受体大鼠。在疾病表现出来之后， 取自这些大鼠的白血病脾细胞再次用于 移植以维持体内白血病细胞系。这个 日本血吸虫各器官和细胞的形态和生化反应 移植的大鼠的特征是更好地辨别 年龄诱发白血病和化学增强型白血病之间的关系。肿瘤 形态、细胞生化、癌基因表达和 移植病例相似，但肿瘤形成时间缩短 从18个月到2个月不等。其准确性和敏感度 应用移植模型预测白血病的长期疗效 在用两种化学物质进行的短期化验中得到确认 (2-乙氧基乙醇、4-己基间苯二酚)下降，三 增加的化学品(吡啶、敌敌畏、2，4，6- 三氯苯酚)前两年白血病患病率 毒性和致癌性研究。与此相关的其他研究 移植模型揭示了两者之间的结构-活性关系 含乙二醇醚结构的化学品及其抑制 白血病的症状。

Up to 30% of the Fischer 344/N strain of rats used in the NTP 2- year toxicity and carcinogenicity studies develop spontaneous leukemia commencing at about 18 months, which reduces the sensitivity for the detection of chemical leukemogenesis. An in vivo cell transplant model was developed to transfer leukemic spleen cells from a rat with spontaneous leukemia into young, healthy recipient rats. After manifestation of the disease, leukemic spleen cells from those rats were again used for transplantation to maintain the leukemic cell line in vivo. The morphological and biochemical responses in organs and cells from the transplanted rats were characterized to better discriminate between age-induced and chemically-enhanced leukemia. The tumor morphology cellular biochemistry, and oncogenetic expressions and transplanted cases were similar, but the time to tumor was reduced from 18 months to 2 months. The accuracy and sensitivity of the transplant model for predicting the long-term leukemogenic potency of chemicals was confirmed in short-term assays with two chemicals (2-ethoxyethanol, 4-hexylresorcinol) that had decreased, and three chemicals that had increased (pyridine, dichlorvos, 2,4,6- trichlorophenol) the prevalence of leukemia in previous 2-year toxicity and carcinogenicity studies. Additional studies with this transplant model revealed structure-activity relationships between chemicals containing the glycol ether structure and the repression of leukemia.