Characteristics of cytochrome P-450 and mixed function oxidase enzymes following treatment with PBBs.

Abstract

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 P1-450 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 P1-450 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 P1-450 inducers, phenobarbital and 3-methylcholanthrene. In addition, the pattern of enzyme induction caused by PBBs in developing rats differs from that in adults, in that the P1-450-associated enzymes are stimulated prior to the P-450-associated 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.

Metabolic activation/deactivation reactions during perinatal development.

“…Neonatal mice which had received kepone and mirex exhibit dramatic elevations in oxidative 0-and N-demethylation pathways (58). The PBBs are also effective transplacental inducers (induction characteristics are mixed with some phenobarbital type induction and some 3-methylcholanthrene type induction) of the hepatic monooxygenase system (59) but are also secreted in high concentrations in milk resulting in increased enzyme activity in pups receiving PBBs only via lactation (59,60). The polychlorinated biphenyls (PCBs) are produced commercially as a mixture of many congeners and are generally considered to be biologically-and ecologically-persistent industrial pollutants.…”

Menstrual function among women exposed to polybrominated biphenyls: A follow-up prevalence study

“…Windham et al noted that cycle length may decrease with increasing levels of PCB 187 but not with other congeners [11]. Rat and hamster models for follicular atresia and ovulatory delay with phenobarbital administration have been demonstrated [75-78], and PBB 153 is a phenobarbital-type inducer [27]. Among smokers, folliculotoxic effects of polycyclic aromatic hydrocarbons on primordial oocytes have been implicated in earlier menopause [79-82], while no relation between PBB exposure and time to menopause was found among women in the MFHS [83].…”

“…By weight, FireMaster ® was 54%–68% PBB 153, a non-coplanar congener. Several coplanar congeners were present in the mixture in smaller amounts [22,27]. Serum concentrations of PBB 153, in parts per billion (ppb), were quantified by gas chromatography with electron capture detection using established protocols.…”

Induction of Drug Metabolizing Enzymes in Polybrominated Biphenyl-Fed Lactating Rats and Their Pups

“…A review by Dent of the effects of PBBs on drug metabolizing enzymes is included in this volume (8). These induced microsomes display the properties seen in response to both phenobarbital (Pb) and to 3-methylcholanthrene (MC) (1-7).…”