PHENOBARBITAL INDUCES CYTOSOLIC ACIDIFICATION IN AN ESTABLISHED LIVEREPITHELIAL-CELL LINE

Phenobarbital (PB), a long-acting barbiturate, is also a known tumor p romoter. The mechanism responsible for the promoting effect of PB has not yet been elucidated. Changes in intracellular pH (pH(in)) have bee n associated with both early and late events of multistage carcinogene sis. We conducted this study to evaluate whether PB alters pH homeosta sis. Adult rat liver (ARL) epithelial cells were cultured for 48 h on glass coverslips, loaded with the intracellular pH indicator sNARF-1, and perfused with various concentrations of PB to evaluate its effect on pH(in) Our results show that PB treatment of cultured cells induces a concentration-dependent cytosolic acidification. These results indi cate that its ability to decrease pH(in) may be involved in the mechan ism of tumor promotion by PB.