EVALUATION OF CHEMICAL MYELOTOXICITY USING AN IN VIVO LEUKEMIA TRANSPLANT MODEL

建立F344大鼠白血病细胞移植模型 致癌物的作用机制，并证实两年的数据 必要时进行研究。假设含有这种物质的化学物质 二甲酯基膦酸基是潜在的白血病原检测 此外还有敌百虫，它被证明可以加速 致癌作用.含二乙基农药的进一步研究 二硫代磷酸酯组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 阿特拉津也在这种短期移植模型中进行研究。 因为被怀疑与农场的白血病和淋巴瘤有关 工人们。乙二醇烷基醚作用机理的研究 在白血病移植模型中显示，无论是 乙二醇单甲醚的醛或酸代谢物为 对持续表现出的抗白血病活性负责 母体化学物质。乙二醇单甲醚的进一步研究 醋酸盐表明这种化学物质比母体更有效。 复方制剂在白血病移植中延长肿瘤潜伏期的作用 模特。从白血病大鼠脾中分离出单核白血病细胞 在白血病移植后的不同时间间隔用于 评估选定的原癌基因在肿瘤进展中的作用 致癌。FMS，BCR，FMS，BCR， ABL和SRC，参与分化和增殖的原癌基因 比较了未经治疗的小鼠脾中的白血病细胞。 白血病移植受者与接受 乙二醇单甲醚确定这些潜在的作用 致癌物进展或抑制过程中的原癌基因 流程。白血病细胞培养物也进行了体外试验。 来自F344大鼠、L1210小鼠白血病细胞和HL60人白血病细胞， 这表明母体化合物而不是酸性代谢物 减少添加微摩尔后生长的细胞数量 乙二醇单甲醚的浓度。

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 or 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.