Immunohistochemical evidence for alterations in specific forms of rat hepatic microsomal cytochrome P-450 during acute carbon tetrachloride intoxication.

The response of specific forms of hepatic microsomal cytochrome P-450 to carbon tetrachloride was studied by immunohistochemical techniques in order to assess the localization and specificity of action for this hepatotoxin. Liver sections were taken from control, phenobarbital-pretreated, and 3-methylcholanthrene-pretreated male rats that had received acute (3 hr) treatment with carbon tetrachloride. The liver sections were examined after indirect immunofluorescent labeling with anti-P-450un, anti-P-450a, anti-P-450b, and anti-P-450c. Diminished fluorescence and loss of intracellular homogeneity of fluorescence were found in the centrilobular cells of liver sections from control rats incubated with anti-P-450un, anti-P-450a, and phenobarbital-pretreated, carbon tetrachloride-challenged rats incubated with anti-P-450b. In liver sections from 3-methylcholanthrene-pretreated, carbon tetrachloride-challenged rats incubated with anti-P-450c, fluorescence was diminished in periportal cells but did not show loss of intracellular homogeneity. These results provide immunohistochemical evidence for the differential effect of carbon tetrachloride on specific forms of cytochrome P-450.