Induction of cytochrome p‐450 in the norway rat, rattus norvegicus, following exposure to potential environmental contaminants

Abstract

Cytochrome P‐450 (CYP) induction (consisting of increases in cellular RNA and protein content and associated catalytic activities) occurs predominantly in the liver, but also in small intestine, lung, kidney, and placenta, of Norway rats (Rattus norvegicus.) exposed to certain types of potential environmental contaminants. The specific isoform(s) induced in the rat and the magnitudes of the increases observed depend upon the chemical nature of the xenobiotic. For instance, the predominant isoforms induced by nonhalogenated polycyclic aromatic hydrocarbons, such as petroleum derivatives and coal‐tar constituents such as the benzopyrenes and the anthracenes, are those of the CYP1A subfamily. Poly‐halogenated aromatic hydrocarbons, such as the halogenated dibenzodioxins, dibenzofurans, and biphenyls, may cause the induction of predominantly the CYP1A subfamily, predominantly the CYP2B subfamily, or mixed CYP1A‐ and CYP2B‐type induction, depending upon the halogen substitution pattern. In contrast, the chlorinated hydrocarbon pesticides, such as DDT, dieldrin, chlordane, and mirex, cause almost exclusively the induction of isoforms of the CYP2B (and to a lesser extent the CYP3A) subfamilies. The commonly employed plasticizing agent di‐(2‐ethylhexyl)phthalate elicits predominantly induction of the CYP4A subfamily. Those xenobiotics that would be expected to be the most pervasive environmental contaminants are typically those that have also been found to cause the most profound CYP induction responses. Such chemicals are extremely lipophilic and tend to accumulate in animal tissues, especially fatty tissues such as the liver. The hepatic CYP induction response to such potential environmental contaminants is typical of the animals’ response to lipophilic xenobiotics in general, and serves as a mechanism by which the excretion of such compounds from the body is facilitated.