Transport of reactive metabolites of procarcinogens between different liver cell types, as demonstrated by the single cell microgel electrophoresis assay.
Procarcinogens have to be activated by specific cytochromes before showing adverse effects. Freshly isolated hepatocytes (parenchymal liver cells, PC) are characterized by a high content of such xenobiotic enzymes and are widely used to investigate chemically induced DNA damage. But in many cases liver tumors caused by indirect acting carcinogens can also originate from non-parenchymal liver cells (NPC). We used freshly isolated rat PC and NPC to demonstrate that only PC have activation capacity when treated in vitro with different genotoxic procarcinogens (N-nitrosodimethylamine, NDMA; vinyl chloride, VC). The alkaline single cell microgel electrophoresis assay was applied to measure the genotoxic activity of the activated compounds. In order to test the hypothesis that reactive metabolites can be transported from PC to NPC, we performed additional in vivo studies as well as studies in which PC were incubated together with NPC, only separated by a dialysis tube (in vitro coincubation). The results indicate that reactive metabolites of both NDMA and VC are stable enough to be transported intercellularly from PC to NPC.
Kuchenmeister
F
F
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
Wang
M
M
Klein
R G
RG
Schmezer
P
P
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002469:Cell Separation; D004249:DNA Damage / Q000187:drug effects; D004587:Electrophoresis, Agar Gel / Q000379:methods*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014752:Vinyl Chloride / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D009603:Nitroso Compounds; C008651:4-nitrosodimethylaniline; D014752:Vinyl Chloride