Effect of mouse skin tumor promoters upon [3H]uridine exchange and focus formation in cultures of C3H/10T1/2 mouse fibroblasts

Abstract

The abilities of 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate (4-O-methyl-TPA) and mezerein to promote the process of transformation were evaluated in cultures of C3H/10T1/2 mouse embryo fibroblasts treated with N-methyl-N'-nitro-N-nitrosoguanidine. Mezerein was found to be as potent as the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) for the promotion of focus formation, eliciting a promotion response at concentrations that ranged from 100 to 2500 ng/ml. 4-O-Methyl-TPA (25-2500 ng/ml) did not promote focus formation, but was mitogenic for confluent cultures. The effects of promoting and non-promoting compounds upon intercellular communication were then evaluated to determine if a rapid assay for the inhibition of communication might serve as a surrogate for the relatively long term, labor-intensive cell transformation assay. Inhibited intercellular communication, as measured by inhibition of [3H]uridine exchange between cells, appeared to correlate with the ability of phorbol related compounds to promote transformation. However, the potent promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin did not inhibit [3H]uridine transfer. Inhibition of intercellular communication may thus be diagnostic of the promoting potential of phorbol-related compounds in C3H/10T1/2 cultures, but may not be an appropriate endpoint for the study of carcinogenic dioxins.