ABSTRACT
AIM:To demonstate the expression of human cytochrome P450 3A4 isozyme in the transgenic cell line CHL - 3A4 established in this laboratory. METHODS:Nifedipine (NIF) can induce the reversal of the brug resistance for adriamycin of multidrug resistant(MDR) cell K562r. The NIF is the specific substlate for CYP3A4. To determine the NIF oxidase activity of the transgenic CHL - 3A4 cells by comparing the biological effect of NIF, which preinculbated with or without CHL - 3A4 S9 mix. RESULTS: When the multidrug resistance cell K562r was cultured in medium with NIF (12. 5 ?g? L- 1 ), a calcium channel blocker and specific substrate for CYP3A, it's IC50 for adri- amycin declined from(6.47?0.60) mg ? L- 1 to (0. 89?0. 15) mg? L-1. When cells were cultured in NIF(exactly the same concentration ) pretreated with CHL - 3A4 S9 mix,no reversal of MDR was observed [IC50 for adriamycin is (6.10?0.50) mg? L-1 ] while if NIF was pretreated with CHL S9 or inactivated CHL - 3A4 S9 mix, its biological effect was not deteriorated [IC50 for adriamycin is (0. 32?0.90) and (0.32?0.04) mg?L-1, P
ABSTRACT
We observe changes of activation of hepatic microsomal cytochrome p-450, changes of formation of riug-and N-hydroxylation of 2-acetylaminofluorene, and changes of vitamin D, in the liver which exposed to UV light and expoeed to UV light after being applied by sunscreens. The results of our study are as shown below: 1. The contents of hepatic microsomal cytochrome p-45p of newborn rats were found to be remarkably increase in the group exposed to UV light for 3 weeks (p<0. 001), but such changes were much reduced in the group exposed to UV light for 3 weeks after being applied by sunscreens(p<0.05. p<0.001, ) 2.Cytochrome p-450 induced by UV light was found to be significantly increased ring and N-hydroxylation of 2-acetylarninofluorene known as carcinogenic source for the liver. In the group exposed to UV light for 3 weeks after being applied by sunscreens, both of ring-and N-hydroxylation of 2-acetylaminofluorene were significantly reduced(p<0. 0, p<0. 001). 3, The contents of vitarnin D, in the liver of newborn rats were found to be gradually increased when they were exposed to UV light for 1 week or 3 weeks (p<0. 001), and in the group exposed to UV light after being applied by sunscreens, such changes were reduced remarkably(pg0. (301).