Different responsiveness of hepatic and pulmonary microsomal mixed function oxidases to phenobarbital-type and 3-methylcholanthrene-type polychlorinated biphenyls in rats.

Abstract

Inductive effects of pretreatments with a phenobarbital(PB)-type 2, 4, 5, 2', 4', 5'-hexachlorobiphenyl(HCB), a 3-methylcholantrene(MC)-type 3, 4, 5, 3', 4'-pentachlorbiphenyl(PenCB) and a mixed type polychlorinated biphenyl(PCB) mixture, Kanechlor(KC-)400 as well as PB and MC on the hepatic and pulmonary microsomal mixed function oxidases(MFOs) were examined and compared using male Wistar rats. Hepatic cytochrome P-450(448) content was increased 2- to 4-fold by pretreatment with all inducers tested, whereas the pulmonary content was slightly elevated only by the MC-type(MC and PenCB) and mixed type inducers. Benzphetamine(BZ) N-demethylase activity in the liver was strongly enhanced by the PB-type(PB and HCB) and mixed type inducers, but not affected by MC and suppressed by PenCB. Pulmonary BZ N-demethylation was not affected by pretreatments with the MC-type and mixed type inducers while both PB-type inducers decreased the activity. The PB-type inducers, showing a weak inducibility for aryl hydrocarbon hydroxylase(AHH) in the liver, also diminished the activity in the lung. In contrast, a marked enhancement of AHH activity in both organs was caused by pretreatment with the MC-type and mixed type inducers. AHH activity in both organs from PenCB-treated rats was highly sensitive to alpha-naphthoflavone but almost insensitive to SKF 525-A. These results strongly suggest that the pulmonary MFO in rats in inducible only with MC-type but not with PB-type PCB unlike the hepatic MFO.