Chloroform induction of ornithine decarboxylase activity in rats.
Chloroform is a drinking water contaminant that has been demonstrated to be carcinogenic to mice and rats resulting in an increased incidence of liver and kidney tumors, respectively. The mechanism of chloroform carcinogenicity might be by tumor initiation and/or promotion. Since induction of ornithine decarboxylase (ODC) activity has been proposed as a molecular marker for tumor promoters, we have investigated the effect of chloroform on ODC activity in rats. Chloroform induced a dose-dependent increase of hepatic ODC with an apparent threshold at 100 mg/kg body weight. Female rats were two to four times more susceptible to to chloroform. Upon daily dosing of chloroform for 7 days the liver became less susceptible, with the last dose of chloroform resulting in only 10% of the activity observed after a single dose. Nuclear RNA polymerase I activity was also induced by chloroform. Chloroform, rather than increasing the activity of renal ODC, resulted in a 35% reduction. The induction by chloroform of hepatic ODC activity might be associated with regenerative hyperplasia while the renal carcinogenicity of chloroform could not be demonstrated to be associated with ODC induction.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002273:Carcinogens; D002725:Chloroform / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D002273:Carcinogens; D002725:Chloroform; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase