Different pathways for mitogenic and enzyme induction signal transduction by cytochrome P450 inducers.

The correlation between enzyme induction and cell proliferation caused by inducers of xenobiotic metabolizing enzymes was studied using a cell culture expressing a constitutive level of cytochrome P450 (hepatoma McA RH 7777) and a cell culture in which cytochrome P450 was absent (hepatoma 27). In hepatoma 27 cells, the inducers did not induce the synthesis of xenobiotic metabolizing enzymes but stimulated cell proliferation. Thus, the processes of signal transduction for enzyme induction and for cell proliferation by the inducers are different.

Coordinated regulation of P-glycoprotein activity and cytochrome P-4501A induction in sublines of rat hepatoma McA RH7777 cells with different levels of colchicine resistance.

The constitutive and induced activities of cytochrome P-4501A isoforms in hepatoma McA 7777 sublines with different levels of colchicine (CH) resistance were studied. The higher CH resistance was associated with the elevated functional activity of P-glycoprotein (Pgp). The constitutive level of benzo(a)pyrene hydroxylase and 7-ethoxyresorufin O-deethylase (cytochrome P-4501A-dependent activities) were the same in sublines with different CH resistance levels.