title: Differential effects of renal carcinogens and tumor promoters on growth promotion and inhibition of gap junctional communication in two rat renal epithelial cell lines.
abstract: To evaluate the effects of renal carcinogens and tumor promoters on gap junctional intercellular communication (IC) and colony formation, two rat kidney epithelial cell lines were examined in vitro. The NRK-52E line was obtained from the American Type Culture Collection and the NK-4 line was established by us from male F344/NCr rats. The NRK-52E line was co-cultured on a confluent monolayer of lethally irradiated NRK-52E cells to determine colony-forming ability (cloning efficiency) and clonal expansion (average surface area of the colonies, SA) and the NK-4 line was cultured on collagen gel. Streptozotocin (STZ), a renal carcinogen, and trisodium nitrilotriacetate monohydrate (NTANa3), a renal carcinogen and tumor promoter, showed mild growth-enhancing effects on both cell lines, as determined by significant increases in SA, but not in cloning efficiency (CE). Sodium barbital (BBNa), a renal tumor promoter, had similar effects, while phenobarbital sodium (PBNa), a non-renal tumor promoter, lacked such activity. The effects of these compounds on gap junctional function were investigated by the Lucifer Yellow dye transfer microinjection assay using monolayers of NRK-52E and NK-4 cells. We found that STZ, NTANa3 and BBNa inhibited IC in NRK-52E cells, in accordance with their reported tumorigenic and/or tumor-promoting activity in vivo, while PBNa did not. Thus, we could present these findings in NRK-52E cells as an in vitro model to examine the potential tissue-specific effects of renal carcinogens and tumor promoters in vitro. We found, however, that other growth control mechanisms beside IC may play a role, because although the NK-4 line did not possess normal IC, the tumor promoters studied had identical growth-promoting effects on colony formation and expansion in both this cell line and the NRK-52E line.
authors: Tumor Pathology and Pathogenesis Section, National Cancer Institute, Frederick, MD 21701-1013.
authors: N
authors: N
authors: Konishi
authors: P J
authors: PJ
authors: Donovan
authors: J M
authors: JM
authors: Ward
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001462:Barbital / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D002273:Carcinogens; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002999:Clone Cells; D004848:Epithelium; D006863:Hydrogen-Ion Concentration; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007668:Kidney; D007680:Kidney Neoplasms / Q000139:chemically induced; D008297:Male; D008854:Microscopy, Electron; D009571:Nitrilotriacetic Acid / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D000085:Acetates; D001463:Barbiturates; D002273:Carcinogens; D013311:Streptozocin; D001462:Barbital; D009571:Nitrilotriacetic Acid; D010634:Phenobarbital