Pereira M A, Savage R E, Guion C W, Wernsing P A
Toxicol Lett. 1984 Jun;21(3):357-64. doi: 10.1016/0378-4274(84)90097-3.
Chloroform administered intraperitoneally (i.p.) to male mice and rats resulted in a dose-dependent increase in hepatic ornithine decarboxylase (ODC) activity. Maximal induction of the enzyme in mice was 10-fold and occurred at 375 mg/kg chloroform; in rats it was 52-fold and occurred at 750 mg/kg chloroform. Chloroform increased in mice and decreased in rats the rate of hepatic and renal DNA synthesis. Therefore, the induction of ODC activity in rat liver was not followed with an increase in DNA synthesis. The implications of these results to the proposed nongenetic mechanism of chloroform induction of hepatocellular carcinoma in mice and renal tumors in rats are discussed.
给雄性小鼠和大鼠腹腔注射氯仿后,肝脏鸟氨酸脱羧酶(ODC)活性呈剂量依赖性增加。小鼠中该酶的最大诱导倍数为10倍,在氯仿剂量为375mg/kg时出现;大鼠中为52倍,在氯仿剂量为750mg/kg时出现。氯仿使小鼠肝脏和肾脏的DNA合成速率增加,使大鼠的该合成速率降低。因此,大鼠肝脏中ODC活性的诱导并未伴随DNA合成增加。讨论了这些结果对所提出的氯仿诱导小鼠肝细胞癌和大鼠肾肿瘤的非遗传机制的意义。