Tennekes H A, Wright A S, Dix K M, Koeman J H
Cancer Res. 1981 Sep;41(9 Pt 1):3615-20.
The effects of naturally occurring microsomal enzyme inducers on hepatocellular drug-metabolizing enzyme systems and also upon the incidence of "spontaneous" liver tumors in CF-1 mice were investigated, using animals maintained on semisynthetic diet and filter-paper bedding as controls. The administration of dieldrin, a potent microsomal enzyme inducer with tumorigenic properties in livers of CF-1 mice, to some of the experimental treatment groups served as a positive control. Conventional diet and sawdust bedding caused induction of the liver monooxygenase system, although this effect was far less pronounced than that produced by dieldrin. The incidence of liver tumors in mice exposed to conventional diet and sawdust bedding was similar to that seen in the control group. The incidence of liver tumors was significantly increased in dieldrin-treated mice, including those maintained on semisynthetic diet and filter-paper bedding. Both benign and malignant tumors were found in dieldrin-treated mice, the latter type of lesion showing evidence of lung metastasis. These results, together with evidence that dieldrin and its mammalian metabolites possess neither genotoxic activity nor potential, are consistent with the concept that dieldrin exacerbates or facilitates the expression of a preexisting oncogenic factor which is genetically linked and possibly viral in origin.
使用以半合成饲料和滤纸垫料饲养的动物作为对照，研究了天然存在的微粒体酶诱导剂对CF-1小鼠肝细胞药物代谢酶系统以及“自发”肝肿瘤发生率的影响。向一些实验治疗组给予狄氏剂，一种在CF-1小鼠肝脏中具有致瘤特性的强效微粒体酶诱导剂，作为阳性对照。常规饲料和木屑垫料会诱导肝脏单加氧酶系统，尽管这种作用远不如狄氏剂产生的作用明显。暴露于常规饲料和木屑垫料的小鼠肝肿瘤发生率与对照组相似。狄氏剂处理的小鼠，包括以半合成饲料和滤纸垫料饲养的小鼠，肝肿瘤发生率显著增加。在狄氏剂处理的小鼠中发现了良性和恶性肿瘤，后者显示出肺转移的迹象。这些结果，连同狄氏剂及其哺乳动物代谢产物既不具有遗传毒性活性也不具有遗传毒性潜力的证据，与狄氏剂加剧或促进预先存在的致癌因子表达的概念一致，该致癌因子与遗传相关且可能起源于病毒。
