Susceptibility of skin fibroblasts from individuals genetically predisposed to cancer, to transformation by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate

Abstract

Skin fibroblasts from patients with hereditary retinoblastoma (RB) and familial polyposis coli (FPC) were chosen for study since their predisposition to the tumour may be due to an inherited "initiation" event which is present in every cell. Thus, it might be predicted that skin fibroblasts from these patients would exhibit increased susceptibility to in vitro transformation by tumour promoters alone. In the case of skin fibroblasts from RB patients, transformation as assessed by the ability of the cells to grow in semi-solid medium and their migration in collagen gels did not occur. However, experiments involving skin fibroblasts from FPC patients showed certain of these cells to grow in semi-solid medium following treatment with the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) alone, although the pattern of migration of the parent cell population in collagen gels was unchanged and they were non-tumorigenic in nude mice. The clones which grew in semi-solid medium, although stable with regard to anchor-age-independent growth, were also unaltered in terms of their migration pattern in collagen gels and their tumorigenicity in nude mice, and were considered not to be completely transformed. Parallel cytogenetic analysis showed that, during the course of these transformation studies, TPA significantly increased not only tetraploidy but also the chromosome aberration frequency. Several quadriradial figures were noted.