Familial polyposis coli: growth characteristics of karyotypically variable cultured fibroblasts, response to epidermal growth factor and the tumour promoter 12-0-tetradecanoyl phorbol-13-acetate

Abstract

Growth in low serum and cell saturation density was investigated in 20 skin fibroblast cultures from 17 patients with the autosomal dominant cancer prone condition, familial polyposis coli (FPC). Compared with non-fetal control cultures, the grouped FPC cultures showed significantly better growth in low serum and approximately 30% increase in saturation density. Neither of these properties was correlated with high tetraploidy or clonal rearrangement of the chromosomes. No difference in response to epidermal growth factor was demonstrable between cultures from normal and affected subjects. The tumour promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), had no differential effect on growth in high and low density cultures of FPC and normal cells in short term experiments; both cell types displayed a biphasic response to the agent at low cell density. However, in long term experiments FPC skin cultures showed growth stimulation and greater resistance to the toxic effects of TPA than normal cells. Cells from both fetal and non-fetal controls as well as from FPC subjects displayed anchorage independent growth after treatment with TPA, but in general FPC cultures from skin and colon responded to a greater extent than non-fetal controls. Marked change in tetraploidy after treatment was evident only in those FPC and control cultures which were highly chromosomally abnormal. Both groups showed a slight increase in stable and unstable chromosome rearrangements with treatment but one FPC culture became totally chromosomally abnormal and cloned in agar with high efficiency, as did one of the treated fetal controls which, however, had normal chromosomes.