Phenobarbital induces cytosolic acidification in an established liver epithelial cell line

Phenobarbital (PB), a long-acting barbiturate, is also a known tumor promoter. The mechanism responsible for the promoting effect of PB has not yet been elucidated. Changes in intracellular pH (pHin) have been associated with both early and late events of multistage carcinogenesis. We conducted this study to evaluate whether PB alters pH homeostasis. 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 pHin. Our results show that PB treatment of cultured cells induces a concentration-dependent cytosolic acidification. These results indicate that its ability to decrease pHin may be involved in the mechanism of tumor promotion by PB.