EVALUATION OF CHEMICAL MYELOTOXICITY USING AN IN VIVO LEUKEMIA TRANSPLANT MODEL

建立了F344大鼠白血病移植模型。 在已确定的肿瘤模型中探讨致癌机制(S) 并帮助区分年龄诱导和化学增强 白血病。回顾分析表明，对乙酰氨基酚的化学成分 缩短肿瘤潜伏期，加速白血病的表达 仅在女性中，但在男性移植受者中不存在。一个 丙二醇组分潜在关联性的前瞻性分析 单甲醚和白血病也进行了评估：没有影响 任何剂量水平的化学物质对白血病大鼠肿瘤进展的影响 移植。环己酮肟和丁酮肟对人体健康的影响 乙二醇烷基醚毒性为阴性，尽管有报道称 肟可能会干扰乙醚向酒精的新陈代谢，因此 增强毒性。磷酸二甲酯的构效关系研究 是因为这些化学物质被证明与 白血病发病率的增加。关于移植的其他研究 化验处理了以下化学物质的结构-活性关系 白血病趋势为阴性。黄曲霉的醛和酸代谢物 乙二醇单甲醚(2-ME)对小鼠肿瘤进展无影响 白血病移植模型：抗白血病活性仅限于 母体化合物，2-ME。因为苯胺衍生物降低了 白血病的发病率和脾是肿瘤的主要部位 扩散。构效关系的研究进展 对氯苯胺、盐酸或N，N-二甲基苯胺、脾纤维化和 白血病就开始了。

A leukemia transplant model for F344 rat leukemia was developed to investigate the mechanism(s) of carcinogenicity in a defined tumor model and to help discriminate between age-induced and chemically-enhanced leukemia. Retrospective analyses acetaminophen suggested that the chemical reduced the tumor latency period and accelerated the expression of leukemia only in the female, but not in the male transplant recipients. A prospective analysis of the potential association between propylene glycol monomethyl ether and leukemia was also evaluated: there was no effect of the chemical at any dose level on tumor progression in rats given leukemia transplant. The influence of cyclo-hexanone oxime or butanone oxime on glycol alkyl ether toxicity were negative, even though it was reported that oximes might interfere with the metabolism of ethers to alcohol and thus enhance toxicity. Structure-activity studies of dimethyl phosphate esters were continued because these chemicals were shown to be associated with increased incidences of leukemia. Additional studies with the transplant assay addressed structure-activity relationships for chemicals that were negative for leukemic trends. The aldehyde and acid metabolites of ethylene glycol monomethyl ether (2-ME) did not affect tumor progression in the leukemia transplant model: the anti-leukemic activity was restricted to the parent compound, 2-ME. Because aniline derivatives reduced the incidence of leukemia and the spleen is a primary site for the tumor proliferation. Investigations of the structure-activity relationships between p-chloraniline, HCI or N, N-dimethylaniline, splenic fibrosis, and leukemia were begun.