Potential Role of Bioactivation in Tumor Promotion: Indirect Evidence from Effects of Phenol, Sodium Cyclamate and Their Metabolites on Metabolic Cooperation In vitro

摘要

Current scientific opinion appears to be that bioactivation is not of general importance in tumor promotion. Recent studies of inhibition of metabolic cooperation (exchange of low molecular weight substances through gap junctions) between cultured mammalian cells by selected tumor promoters and their metabolites suggest that the promoting effects of some chemicals might occur through metabolic products. Phenol and sodium cyclamate are cases in point. Studies conducted in the laboratory show that phenol, a promoter of mouse skin tumors, fails to inhibit metabolic cooperation between Chinese hamster V79 cells; however, five metabolites of phenol suppress metabolic cooperation in a concentration-related fashion. In similar studies, soodium cyclamate, a possible promoter of bladder cancer in rats, is a weak inhibitor of metabolic cooperation between V79 cells, but three metabolics of sodium cyclamate are stronger inhibitors. These results suggest that metabolism might be a factor in the tumor-promoting activity of some agents.