Development of in vitro systems for chemoprevention research.
The C3H/10T1/2 mouse fibroblast cell line has been developed as a predictive model for cancer chemopreventive agents. The retinoids, which are currently being evaluated as chemopreventive agents in the clinic, are potent inhibitors or chemically induced neoplastic transformation in this cell line. Mechanistic studies suggest that retinoids stabilize chemically initiated cells and prevent their transformation by enhancing gap junctional communication between these cells and adjacent growth-inhibited normal 10T1/2 cells. Carotenoids also prevent chemically and physically induced neoplastic transformation of 10T1/2 cells. beta-Carotene is active without evidence of bioconversion to retinoids, implying that this dietary constituent has intrinsic chemopreventive activity. This cell culture system mimics many aspects of carcinogenesis in animals and man and appears well suited to mechanistic studies at the cellular and molecular level.