Differential modulation of hepatic cytochrome P-450 enzymes in rat and syrian hamster by 4′-trifluoromethyl-2,3,4,5-tetrachlorobiphenyl
✍ Scribed by Bani, Marie-Hélène ;Narbonne, Jean-Franc??is ;Fukuhara, Morio ;Ushio, Fusao ;Robertson, Larry W.
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 871 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0887-2082
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✦ Synopsis
Abstract
The effects of a single injection (40 mg/kg) of 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl (CF3) on hepatic cytochrome P‐450 monooxygenases were assessed in rat and syrian hamster. The CF3 treatment significantly increased the total amount of cytochrome P‐450 in both species. In rats, CF3 treatment caused marked increases in ethoxyresorufin O‐deethylase (EROD), arylhydrocarbon hydroxylase (AHH), and testosterone 7α‐hydroxylase activities but significantly reduced the activities of benzphetamine N‐demethylase (BzND), erythromycin N‐demethylase (ErND), testosterone 6β, 16α, and 16β‐hydroxylases, and formation of androstenedione. Administration of CF3 to hamsters strongly induced the activities of EROD, AHH, BzND, testosterone 15α, and 16α‐hydroxylases, and androstenedione production, whereas ErND, testosterone 6β, and 7α‐hydroxylases were decreased. Administration of CF3 to rats induced the CYP1A family proteins and CYP2A1, while CF3 reduced the level of CYP2B1, and, to a lesser extent, of CYP6β2. In hamsters, CF3 treatment significantly induced the CYP1A2, CYP2A1, CYP2A8, and CYP2B1 isozymes, whereas the CYP6β2 level was decreased. The ability of hepatic microsomes to activate aflatoxin B1 and benzo(a)pyrene was elevated by CF3 treatment in hamsters, while activation of aflatoxin B1 was decreased in microsomes from CF3‐treated rats. These results showed differences in the CF3‐induced pattern of rat and hamster cytochrome P‐450 monooxygenases.