Saccharin may act as a tumour promoter by inhibiting metabolic cooperation between cells

The possible role of saccharin in the carcinogenic process is, at present, still unclear. Carcinogenesis is a complex process involving, in many test systems, initiation and promotion phases 1 . Current evidence favours the hypothesis that initiation is due to a mutagenic event, while promotion (at least the early portion) is the result of epigenetic changes 2 . Although saccharin has been reported to be a weak mutagen in various in vitro test systems and a weak initiator in mouse skin 3–7 , there is increasing evidence from in vitro , as well as in vivo , studies that it might act as a tumour promoter 8–13 , rather than as a mutagen 14–19 . Recently, L.P.Y. et al. 20 and J.E.T. et al. 21 developed an in vitro assay to detect tumour promoters, which has been independently reported by Murray and Fitzgerald 22 . The assay is based on the principle that phorbol ester-type tumour promoters block ‘metabolic cooperation’ or a type of cell–cell communication between cells. We report here a series of experiments demonstrating the elimination of metabolic cooperation in the hypoxanthine guanine phosphoribosyltransferase (HGPRT) system in Chinese hamster V79 cells, indicating that saccharin shares properties similar to those of other known promoters.