Chloroform induction of ornithine decarboxylase antizyme (ODC-AZ) in male rat liver.

Chloroform stimulation of rat hepatic ODC is most dramatic at 18 h following a single injection. Repeated dosing, 1 dose/d for up to 7 d, results in a daily decline in the ability of the liver enzyme to respond 18 h after the final injection. We postulated that this decline was due to an increased synthesis and accumulation of the OCD-AZ protein. ODC-AZ was determined by measuring the inhibition of isolated ODC activity as described by Hayashi and Fujita and modified in our laboratory to use kidney ODC. Male and female Fischer 344 rats were injected daily for 1, 3, or 7 d with 3.0 mmol/kg chloroform. Chloroform induced ODC-AZ activity in males at 3 and 7 d (26% and 37% inhibition of the ODC activity in the incubation medium, respectively). While females exhibited a similar decline in ODC activity after repeated doses, ODC-AZ was not induced. Thus, it would appear that daily exposure of rats to chloroform results in a refractoriness of its induction of ODC activity accompanied by an induction of the ODC-AZ in males. However, in females these two responses were not directly related.