Polychlorinated biphenyls enzyme induction

For halogenated aromatic hydrocarbons like polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) the binding to the aryl hydrocarbon (Ah) receptor regulates their toxicity [89]. The Ah receptor controls the induction of one of the cytochrome P450 enzymes in the liver. Toxic responses such as thymic atrophy, iveight loss, immu-notoxicity and acute lethality are associated ivith the relative affinity of PCBs, PCDFs and PCDDs for the Ah receptor [89]. The quantitative structure-activity relationship (QSAR) models predicting the affinity of the halogenated aromatic hydrocarbons ivith the Ah receptor describe the electron acceptor capability as well as the hydrophobicity and polarizability of the chemicals [89[. 

Buckman, A.H. Brown, S.B. Small, J. Muir, D.C.G. Parrott, J. Solomon, K.R. Fisk, A.T., Role of temperature and enzyme induction in the biotransformation of polychlorinated biphenyls and bioformation of hydroxylated polychlorinated biphenyls by rainbow trout Oncorhynchus mykiss). Environ Sci. Technol. 2007, 41, 3856-3863. 

Kato Y, Haraguchi K, Kawashima M, et al. 1995. Induction of hepatic microsomal drug-metabolizing enzymes by methylsulphonyl metabolites of polychlorinated biphenyl congeners in rats. Chem Biol Interact 95 257-268. 

The most popular system at the present time may be that of activation by microsomal extracts. This procedure calls for the use of a mammalian organ homogenate to provide for mammalian metabolism in the presence of the test compound. The most popular system, which Ames et al have called the S-9 fraction, utilises supernatants of rat liver homogenates centrifuged at 9000 g. It has been suggested that induction of rat liver enzymes with a polychlorinated biphenyl increases the sensitivity of the system. This can be accomplished by a single intraperitoneal injection 5 days prior to the preparation of the homogenates. 

---