Induction of Cytochrome P-450 in Rat Liver After Inhalation of Aromatic Organic Solvents

Abstract

Organic solvents are of great interest in the field of occupational health due to their frequent use in different types of industries. It is now evident that effects such as hepatotoxicity and carcinogenicity are the results of metabolic activation occurring in the body. This has been shown for the hepatotoxicity and carcinogenicity of carbon tetrachloride, chloroform, and trichloroethylene (Banerjee and Van Duuren 1978; Moslen et al. 1977;Sipes et al. 1977), the carcinogenicity of dioxane (Woo et al. 1978), the hepatotoxicity of carbon disulfide (Dalvi et al. 1975; Dalvi et al. 1974; Magos and Butler 1972), as well as the leukemogenic effect of benzene (Laskin and Goldstein 1977) and the neurotoxicity of n-hexane and methyl n-butyl ketone (Couri et al. 1978; Schaumburg and Spencer 1978). The enzyme system responsible for this activation through the formation of epoxides or other reactive metabolites is in most cases the liver microsomal cytochrome P-450-dependent system. The activity of this enzyme system, which consists of separate isoenzymes with different substrate specificities (Toftgård et al. 1980; Haugen and Coon 1976) can be modulated by exogenous factors, including exposure to hydrocarbon solvents. This may lead to an altered susceptibility to the toxic effects of the solvent itself or to other environmental contaminants. An inducing effect on the liver microsomal cytochrome P-450 in rats has been shown after inhalation of methylchloroform, benzene, carbon tetrachloride, and trichloroethylene (Norpoth et al. 1974; Fuller et al. 1970).