EVALUATION OF CHEMICAL MYELOTOXICITY USING AN IN VIVO LEUKEMIA TRANSPLANT MODEL

建立了F344大鼠白血病细胞移植模型， 研究致癌物质的作用机制，并证实 必要时提供2年研究数据。 的假设 含有二甲基酯膦酸基团的化学品， 用敌百虫进一步测试了潜在的致白血病物质， 显示加速致癌过程：进一步研究， 含有二乙基二硫代磷酸酯基团的农药， 正在使用白血病移植模型来确定 这种肿瘤诱导的特异性。 杀虫剂阿特拉津也被 在这种短期移植模型中进行了研究，因为怀疑 与农场工人的白血病和淋巴瘤有关。 研究 二醇烷基醚的作用机制继续，它是 在白血病移植模型中显示， 乙二醇单甲醚的酸性代谢产物是负责 对于母体药物始终表现出的抗白血病活性 化工有限 乙二醇单甲醚乙酸酯的进一步研究 表明这种化学物质比母体化合物更有效 在白血病移植模型中延长肿瘤潜伏期。 从白血病大鼠脾脏中分离的单核细胞白血病细胞 使用白血病移植后的不同时间间隔， 评估选定的原癌基因在肿瘤进展过程中的作用， 致癌作用 FMS，BCR， ABL和SRC，参与分化的原癌基因， 增殖的白细胞，比较在白血病细胞从脾 未经治疗的白血病移植受者与那些来自受者 用乙二醇单甲醚处理，以确定电位 这些原癌基因的作用，在发展ofr抑制 致癌过程。 还进行了体外试验， 来自F344大鼠的白血病细胞培养物。 L1210小鼠白血病细胞，和 HL 60人白血病细胞，这表明母体化合物 而不是酸性代谢物减少生长细胞的数量后， 加入微摩尔浓度的乙二醇单甲基 乙醚

A cell transplant model for F344 rat leukemia was developed to investigate the mechanism of action of carcinogens, and to corroborate data from 2-year studies when necessary. The hypothesis that chemicals containing the dimethyl ester phosphonic acid group were potential leukemogens was tested further with trichlorfon, which was shown to accelerate the process of carcinogenesis: further studies with pesticides containing the diethyl dithiophosphate ester group are underway using the leukemia transplant model to determine the specificity of this tumor induction. The pesticide atrazine is also being investigated in this short-term transplant model since it is suspected to be associated with leukemia and lymphoma in farm workers. Studies of the mechanism of action of glycol alkyl ethers continued, and it was shown in the leukemia transplant model that neither the aldehyde or acid metabolites of ethylene glycol monomethyl ether were responsible for the anti-leukemic activity consistently exhibited by the parent chemical. Further studies with ethylene glycol monomethyl ether acetate showed that this chemical was more effective than the parent compound in extending the tumor latency period in the leukemia transplant model. Mononuclear leukemia cells separated from spleens of leukemic rats at various intervals following leukemia transplantation were used to evaluate the role of selected protooncogenes during the progression of carcinogenesis. The pattern of expression or inactivation of FMS, BCR, ABL, and SRC, protooncogenes involved in differentiation and proliferation of leukocytes, was compared in leukemic cells from spleens of untreated leukemic transplant recipients with those from recipients treated with ethylene glycol monomethyl ether to determine the potential role of these protooncogenes during the progression ofr inhibition of the carcinogenic processes. In vitro tests were also conducted with leukemic cell cultures from F344 rats. L1210 mouse leukemia cells, and HL60 human leukemia cells, which indicated that the parent compound but not the acid metabolite reduced the numbers of growing cells after addition of micromolar concentrations of ethylene glycol monomethyl ether.