DIFFERENTIAL MODULATION OF HEPATIC CYTOCHROME-P-450 ENZYMES IN RAT AND SYRIAN-HAMSTER BY 4'-TRIFLUOROMETHYL-2,3,4,5-TETRACHLOROBIPHENYL

The effects of a single injection (40 mg/kg) of 4'-trifluoromethyl-2,3 ,4,5-tetrachlorobiphenyl (CF3) on hepatic cytochrome P-450 monooxygena ses were assessed in rat and syrian hamster. The CF3 treatment signifi cantly increased the total amount of cytochrome P-450 in both species. In rats, CF3 treatment caused marked increases in ethoxyresorufin 0-d eethylase (EROD), arylhydrocarbon hydroxylase (AHH), and testosterone 7 alpha-hydroxylase activities but significantly reduced the activitie s of benzphetamine N-demethylase (BzND), erythromycin N-demethylase (E rND), testosterone 6 beta, 16 alpha, and 16 beta-hydroxylases, and for mation of androstenedione. Administration of CF3 to hamsters strongly induced the activities of EROD, AHH, BzND, testosterone 15 alpha; and 16 alpha-hydroxylases, and androstenedione production, whereas ErND, t estosterone 6 beta, and 7 alpha-hydroxylases were decreased. Administr ation of CF3 to rats induced the CYP1A family proteins and CYP2A1, whi le CF3 reduced the level of CYP2B1, and, to a lesser extent, of CYP6 b eta 2. In hamsters, CF3 treatment significantly induced the CYP1A2, CY P2A1, CYP2A8, and CYP2B1 isozymes, whereas the CYP6 beta 2 level was d ecreased. The ability of hepatic microsomes to activate aflatoxin B1 a nd benzo(a)pyrene was elevated by CF3 treatment in hamsters, while act ivation of aflatoxin B1 was decreased in microsomes from CF3-treated r ats. These results showed differences in the CF3-induced pattern of ra t and hamster cytochrome P-450 monooxygenases.