Selective cytotoxicity of N-nitrosamines to cultured rat esophageal epithelial cells.
The rat esophageal carcinogen N-nitrosomethylbenzylamine was shown to be highly toxic to rat esophageal epithelial (REE) cells in short-term primary culture. A significant level of cell killing could be observed at 10(-6) M. Several other esophageal carcinogens were also cytotoxic in a dose-dependent manner. Nitrosamines that do not produce esophageal tumors in the rat were generally unable to kill the esophageal cells. The results demonstrate that REE cells retain their metabolic capacity to activate specific nitrosamines to toxic metabolites. The culture system will be useful for mechanistic studies on the tissue specificity of these carcinogens, as well as to search for environmental agents that kill esophageal cells that may be involved in the causation of esophageal cancer.
Zucker
P F
PF
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Canada.
Giles
A
A
Chaulk
E J
EJ
Archer
M C
MC
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D004947:Esophagus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
D002273:Carcinogens; D009602:Nitrosamines; D013778:Tetrazolium Salts; D013844:Thiazoles; C014707:nitrosobenzylmethylamine; C022616:thiazolyl blue; D014343:Trypan Blue; D004128:Dimethylnitrosamine; D004121:Dimethyl Sulfoxide