• Analysis of spontaneous, carcinogen-induced and promoter-induced chromosomal instability in patients with hereditary retinoblastoma.

      Gainer, H S; Kinsella, Anne R; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX (1983-10-15)
      Skin fibroblasts from patients with hereditary retinoblastoma (RB cells) were examined since predisposition to the tumour might be expected to involve some degree of chromosomal instability, as has been noted for several cancer-prone conditions. Spontaneous and N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced aberration frequencies were measured, the cytogenetic effects of long-term treatment with 12-O-tetradecanoyl-phorbol-13acetate (TPA) were examined and also the spontaneous and TPA-induced sister chromatid exchange (SCE) frequencies. In all the studies the RB cells behaved in a similar fashion to normal human skin fibroblasts.
    • Susceptibility of skin fibroblasts from individuals genetically predisposed to cancer, to transformation by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate.

      Gainer, H S; Schor, Seth L; Kinsella, Anne R; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Wilmslow Road, Withington, Manchester M20 9BX, UK (1984-09-15)
      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.