Effect of Hydrocortisone on the Proliferation of Cultured Skin Fibroblasts from Normal Individuals and Individuals at High Risk of Colon Cancer

Abstract

In the present study we have compared the mitogenic effects of hydrocortisone (HC), both in the cloning efficiency (CE) assay and in semisolid agar, on skin fibroblasts (SF) obtained from individuals with hereditary adenomatosis of the colon and rectum (ACR) and their age-matched controls. The maximum stimulation of both cell types in the CE assay occured at an HC concentration of 500 ng/ml, but normal adult SF (NSF) were more sensitive to the mitogenic effects of HC than were ACR SF. The stimulation of cell proliferation in agar by HC (range 0–20 µg/ml) was apparently maximal at about 5 µg/ml of HC. However, NSF proliferated in agar containing HC considerably better, proportionately, than did ACR cells, whereas no growth of normal cells in agar was seen in the absence of HC. Normal neonatal foreskin fibroblasts (FOS) and colon adenocarcinoma cells (HT-29), in that order, were increasingly more refractory to the proliferative effects of HC in both the CE assay and in semi-solid agar. Charcoal-treated serum (from which steroids were largely removed) supported to a varying degree the growth of colon adenocarcinoma cells, FOS and ACR SF, but not of NSF cells. On the other hand, addition of HC to charcoal-treated serum primarily stimulated the proliferation of NSF cells. The reduced sensitivity of ACR SF to HC may be closely linked to mechanisms associated with initiation and promotion for this form of cancer.