Characteristics of Cytochrome P-450 and Mixed Function Oxidase Enzymes Following Treatment with PBBs

Abstract

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org. . The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives. The mixture of PBBs in FireMaster BP-6 has been demonstrated to constitute potent inducers of hepatic and extrahepatic mixed function oxidase (MFO) enzymes. Chronic dietary administration of PBBs to mature female rats results in a "mixed" pattern of induction, with increases in both cytochrome P-450 and P,-450 associated enzymes. Acute administration of PBBs (150 mg/kg IP) to mature female rats resulted in a time-dependent induction of MFO activities; the P-450-dependent enzymes were simulated early (24-48 hr after administration) while the P,-450 dependent enzymes reached maximal activities at later time points. However, studies of the kinetics and patterns of inhibition of the induced enzymes along with gel electrophoresis studies of the microsomal proteins indicate that PBBs may induce different proteins from those induced by the classical P-450 and P,-450 inducers, phenobarbital and 3methylcholanthrene. In addition, the pattern of enzyme induction caused by PBBs in developing ratsdiffers from that in adults, in that the P,-450-associated enzymes are stimulated prior to the P-450associated enzymes. The overall pattern of enzyme induction in extrahepatic tissue differs from that seen in the liver and sex differences in enzyme induction have also been demonstrated. As modifications of MFO activity may alter the toxicity of chemicals, these findings suggest that the toxicity of chemicals may be altered in animals exposed to PBBs and that these toxicities may exhibit age, sex, and organ specificities different from those seen in control animals.

Exposure to polybrominated biphenyl and stochastic epigenetic mutations: application of a novel epigenetic approach to environmental exposure in the Michigan polybrominated biphenyl registry

“…Enrichment of these pathways in multiple participants of the Michigan PBB Registry (especially since they are the only pathways enriched in multiple participants) is of interest because scale for ease of interpretation, but the statistical analysis was done as described in methods. cytochrome 450 was observed to be upregulated in rats after they were exposed to PBB [48][49][50], and altered steroid hormone levels and endocrine disruption was found to be associated with PBB exposure, both in animal models [51][52][53] and in epidemiological studies [23,24,54,55]. Even though there was no enrichment of these pathways in people with increased exposure compared to other people in this study, part of this could be because of the extremely high PBB exposure in this population (median exposure is 27 times higher than the national average), thus making it a comparison of high exposure to higher exposure [22].…”

Environmental intoxicants and their fundamental interactions

“…Human exposure resulted from the consumption of PBB contaminated meat, dairy products, and eggs and represented the first known instance of human ingestion of PBB. PBB's are potent inducers of the microsomal oxidase system (Blumberg, 1978), by means of which some of these xenobiotics are modified and excreted (Dent, 1978). Strong interactions between PBB's and other such inducers, such as those of dietary origin, have been observed (Babish, Stoensand & Lisk, 1978).…”