TRANSPORT OF REACTIVE METABOLITES OF PROCARCINOGENS BETWEEN DIFFERENTLIVER-CELL TYPES, AS DEMONSTRATED BY THE SINGLE-CELL MICROGEL ELECTROPHORESIS ASSAY

Procarcinogens have to be activated by specific cytochromes before sho wing adverse effects. Freshly isolated hepatocytes (parenchymal liver cells, PC) are characterized by a high content of such xenobiotic enzy mes and are widely used to investigate chemically induced DNA damage. But in many cases liver tumors caused by indirect acting carcinogens c an also originate from non-parenchymal liver cells (NPC). We used fres hly isolated rat PC and NPC to demonstrate that only PC have activatio n capacity when treated in vitro with different genotoxic procarcinoge ns (N-nitrosodimethylamine, NDMA; vinyl chloride, VC). The alkaline si ngle cell microgel electrophoresis assay was applied to measure the ge notoxic activity of the activated compounds. In order to test the hypo thesis that reactive metabolites can be transported from PC to NPC, we performed additional in vivo studies as well as studies in which PC w ere incubated together with NPC, only separated by a dialysis tube (in vitro coincubation). The results indicate that reactive metabolites o f both NDMA and VC are stable enough to be transported intercellularly from PC to NPC.