MODULATORY EFFECT OF PIPERINE ON BENZO[A]PYRENE CYTOTOXICITY AND DNA ADDUCT FORMATION IN V-79 LUNG FIBROBLAST CELLS

Piperine, a major component of black pepper and long peppers, has been reported previously to have an effect on the activation and deactivation of some exogenous substances. In the present study, piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (B[a]P) in cultured V-79 lung fibroblast cells. The V-79 cells were treated with a non-toxic dose of piperine (1-20 mu M) plus 10 mu M B[a]P, or pretreated with piperine for 30 min or 2 hr prior to the administration of 10 mu M B[a]P. B[a]P cytotoxicity was potentiated significantly by piperine under each experimental condition. The relative plating efficiency (RPE) was 71% when V-79 cells were exposed to 10 mu M B[a]P alone. When the culture was exposed to B[a]P plus piperine or pretreated with piperine for 30 min prior to the administration of B[a]P, the RPE values were 63 and 44% (P < 0.001), respectively. Pretreatment with piperine for 2 hr had no significant effect (P > 0.05). Furthermore, the lowest activities (P < 0.05) of glutathione S-transferase (GST) and uridine diphosphate glucuronyl transferase (UDP-GTase) of piperine-treated V-79 cells occurred 30 min to 1 hr after the piperine pretreatment. Pretreatment of V-79 cells with piperine also caused an increase in the covalent binding of B[a]P-diol-epoxide to DNA, 2.3 times greater than that of the V-79 cells without piperine treatment. These results suggest that the promotion by piperine of B[a]P-induced cytotoxicity in V-79 lung fibroblast cells is due to mechanisms that decrease the activities of GST and UDP-GTase and increase the formation of a B[a]P-DNA adduct.