Chloroform-induced multiple forms of ornithine decarboxylase: differential sensitivity of forms to enhancement by diethyl maleate and inhibition by ODC-antizyme.
Savage-RE Jr.; Nofzinger-K; Bedell-C; DeAngelo-AB; Pereira-MA
J Toxicol Environ Health 1989 May; 27(1):57-64
The effect of pretreatment with the glutathione depleting agent diethyl-maleate on the chloroform (67663) induction of two different forms of male rat liver ornithine-decarboxylase (ODC) activity, and the sensitivity of the two forms of the enzyme to inhibition by ODC- antizyme (ODC-AZ) were studied in rats. Male Fischer-344-rats were given a 3 hour pretreatment with diethyl-maleate at 325mg/kg, intraperitoneally (ip), prior to chloroform administration at 6.0 nanomoles/kilogram, ip for 18 hours. Treatment of animals with chloroform alone resulted in stimulations of Peak-I and Peak-II activities to a 5.5 and 12.0 fold increase over controls, respectively. Pretreatment with diethyl-maleate followed by the same dose of chloroform resulted in a minor increase in Peak-I but a continued increase in the ODC activity associated with Peak-II of three fold over chloroform alone and 36 fold over controls. With chloroform alone, Peak-II activity constituted 35 percent of the total recoverable ODC activity from the cytoplasm, while pretreatment of animals with diethyl-maleate followed by chloroform resulted in Peak-II activities accounting for 70 percent of the total ODC recoverable activity. The Peak-II form of ODC isolated from male rat liver was slightly more sensitive to ODC-AZ inhibition than was the Peak-I form of the enzyme.
NIOSH-Author; Laboratory-animals; Enzyme-activity; Liver-enzymes; Liver-damage; Hepatotoxicity; Toxic-effects; Chlorinated-hydrocarbons
Journal of Toxicology and Environmental Health