Interaction of tetrachloroethylene with rat hepatic microsomal P450-dependent monooxygenases

Article abstract of DOI:10.3109/00498259509061841

1. We have studied the effects of tetrachloroethylene (PCE) on the kinetics of the P450-dependent monooxygenases in rat liver microsomes. 2. 7-Pentoxyresorufin O-depentylase (PROD) and 7-benzyloxyresorufin O-debenzylase (BROD) activities in phenobarbital (PB)-treated rat liver microsomes were substantially inhibited by PCE. The inhibition profiles were non-competitive for both enzyme activities; K(i)'s from Eadie-Hofsee plots were 0.16 and 0.29 mM for PROD and BROD respectively. In contrast, the enzyme activities in untreated, β-naphthoflavone (BNF)-, isoniazid (ISN)- and pregnenolone-16α-carbonitrile (PCN)-induced microsomes were not affected by PCE. 3. 7-Ethoxycoumarin O-deethylase (ECOD) activity in PB-induced microsomes was competitively inhibited by PCE, with a K(i) that was lower than those of other microsomes. 4. PCE inhibited 7-ethoxyresorufin O-deethylase (EROD) activities in some microsomes slightly. The K(i) for PCE was the lowest in untreated, followed by ISN-treated microsomes. 5. No effect of PCE upon aniline 4-hydroxylase (AN4H) and testosterone 6β-hydroxylase (TS6BH) activities was evident in any microsomal preparation. 6. These results indicate that PCE inhibits PB-inducible, P450-dependent monooxygenases in vitro non-competitively or competitively, and that the P450 enzymes of the P4502B subfamily may contribute to PCE toxicity.

Full text of DOI:10.3109/00498259509061841

Xenobiotica
the fate of foreign compounds in biological systems
ISSN: 0049-8254 (Print) 1366-5928 (Online) Journal homepage: http://www.tandfonline.com/loi/ixen20
Interaction of tetrachloroethylene with rat hepatic
microsomal P450-dependent monooxygenases
N. Hanioka, H. Jinno, A. Takahashi, K. Nakano, R. Yoda, T. Nishimura & M.
Ando
To cite this article: N. Hanioka, H. Jinno, A. Takahashi, K. Nakano, R. Yoda, T. Nishimura & M.
Ando (1995) Interaction of tetrachloroethylene with rat hepatic microsomal P450-dependent
monooxygenases, Xenobiotica, 25:2, 151-165
To link to this article: http://dx.doi.org/10.3109/00498259509061841
Published online: 27 Aug 2009.
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Date: 07 November 2015, At: 22:27