Rat hepatic microsomal cytochrome(s) P-450 induced by polybrominated biphenyls.
Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents.
Rat hepatic microsomal cytochrome(s) P-450 induced by polybrominated biphenyls. Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents.