EXOGENOUS PROTOPORPHYRIN INHIBITS HEP G2 CELL-PROLIFERATION, INCREASES THE INTRACELLULAR HYDROGEN-PEROXIDE CONCENTRATION AND CAUSES ULTRASTRUCTURAL ALTERATIONS

Ultrastructural hepatocellular abnormalities in early stages of erythr opoietic protoporphyria lead to hepatobiliary changes that cause overt liver disease in 5-10% of patients, not infrequently progressing to f ulminant hepatic failure. This cannot be attributed solely to protopor phyrin crystal deposition in the liver. Hepatic redox systems have the refore been postulated as an equivalent for the photoreaction of proto porphyrin. We studied the dark effects of protoporphyrin and hematopor phyrin on HL60 and Hep G2 cells. Cell proliferation and intracellular H2O2 concentrations were assessed and related to the ultrastructural m orphology. The incubation with protoporphyrin and hematoporphyrin resu lted in a dose- and time-dependent inhibition of proliferation indices of Hep G2 cells. Flow cytometric analyses of intracellular H2O2 COli- centrations demonstrated a dose-dependent increase in both cell lines upon incubation with protoporphyrin, Hep G2 cells displayed ultrastruc tural alteration of the endoplasmatic reticulum and plasma membranes. Also 'cell blebbing' occurred. We conclude that exogenous protoporphyr in increases the intracellular H2O2 concentration and exerts a cytotox ic dark effect. This may contribute to the liver injury observed in er ythropoietic protoporphyria.