Hyperphosphorylation of p53 induced by benzene, toluene, and chloroform.

Phorbol 12-myristate, 13-acetate (PMA) is a known protein kinase C activator (PKC); benzene, chloroform, and toluene have also been reported to be PKC activators. We examined the effects of these three solvents on the phosphorylation of p53 in treated cells. Hyperphosphorylated p53 was found when p53 was immunoprecipitated from rat liver epithelial cell extracts treated with any of the solvents or PMA. The solvents also resulted in hyper-phosphorylation of human p53 produced by transfection of Saos-2 cells with a eucaryotic expression vector. Increased phosphorylation of p53 induced by the solvents was also observed through in vitro assays. Hyperphosphorylation of p53 may be involved in tumor promotion by benzene, toluene and chloroform.