Suppression of in vitro chemical transformation by the carcinogenesis-promoting, viable yellow gene Avy.

The presence of the viable yellow Avy and lethal yellow Ay genes has been demonstrated to accelerate the process of tumorigenesis in mice bearing genetically, chemically or virally initiated cells. This promoting effect has been reported in the liver, lung, breast, bladder and skin. Although it has been demonstrated that the accelerated process is associated with systemic, pathophysiologic alterations such as an alteration in the lipogenic pathway, which in turn leads to obesity, alteration in glucose metabolism and/or random immunologic alterations, no examination of the in vitro 'tumorigenic' susceptibility of the cells of animals bearing the yellow genes has yet been reported. In the current study, spontaneous and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced transformation was determined in skin-derived fibroblasts from C57BL/6N-Avy/a mice (Hy) and their black a/a litter mates (B1-). The growth rate of untreated fibroblasts was greater for those from the yellow mice than from the black, while susceptibility to MNNG toxicity was equivalent. However, the rate of spontaneous and chemically induced transformation was consistently and significantly higher in the cells obtained from the black a/a mice than in those from yellow, Avy/a litter mates. These findings, with others from the literature, suggest that the Avy gene may suppress transformation and carcinogenic susceptibility in specific cells, such as fibroblasts, while the systemic effects of the gene are promotional in other cells.