INDUCTION OF CYTOCHROME-P-450 IN THE NORWAY RAT, RATTUS-NORVEGICUS, FOLLOWING EXPOSURE TO POTENTIAL ENVIRONMENTAL CONTAMINANTS

Cytochrome P-450 (CYP) induction (consisting of increases in cellular RNA and protein content and associated catalytic activities) occurs pr edominantly in the liver, but also in small intestine, lung, kidney, a nd placenta, of Norway rats (Rattus norvegicus) exposed to certain typ es of potential environmental contaminants. The specific isoform(s) in duced in the rat and the magnitudes of the increases observed depend u pon the chemical nature of the xenobiotic. For instance, the predomina nt 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. Po ly halogenated aromatic hydrocarbons, such as the halogenated dibenzod ioxins, dibenzofurans, and biphenyls, may cause the induction of predo minantly the CYP1A subfamily, predominantly the CYP2B subfamily, or mi xed CYP1A- and CYP2B-type induction, depending upon the halogen substi tution pattern. In contrast, the chlorinated hydrocarbon pesticides, s uch as DDT, dieldrin, chlordane, and mirex, cause almost exclusively t he induction of isoforms of the CYP2B (and to a lesser extent the CYP3 A) subfamilies. The commonly employed plasticizing agent di-(2-ethylhe xyl)phthalate elicits predominantly induction of the CYP4A subfamily. Those xenobiotics that would be expected to be the most pervasive envi ronmental contaminants are typically those that have also been found t o cause the most profound CYP induction responses. Such chemicals are extremely lipophilic and tend to accumulate in animal tissues, especia lly fatty tissues such as the liver. The hepatic CYP induction respons e to such potential environmental contaminants is typical of the anima ls' response to lipophilic xenobiotics in general, and serves as a mec hanism by which the excretion of such compounds from the body is facil itated.