Opposing effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone on growth and differentiation of cultured malignant human keratinocytes.
The human keratinocyte line SCC-13, derived from a squamous cell carcinoma of epidermis, was examined for effects on growth and differentiation upon treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition of growth was observable at 0.1 nM and maximal in the concentration range of 1-100 nM TCDD, but was completely antagonized by addition of hydrocortisone to the growth medium. TCDD was found to inhibit several aspects of keratinocyte differentiation that are stimulated by hydrocortisone. In confluent cultures, accumulation of keratin protein and transglutaminase activity were suppressed as well as spontaneous envelope formation and envelope competence. This phenomenon occurred without significant effect of TCDD on depletion of hydrocortisone from the medium. We conclude that the response of SCC-13 cells to TCDD depends upon hormonal conditions in culture and that this agent can interfere with cellular responses to normal physiological conditions, thereby altering the differentiation program ordinarily observed.
D000217:Acyltransferases / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004147:Dioxins / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007633:Keratins / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000503:physiopathology*; D011503:Transglutaminases
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D007633:Keratins; D000217:Acyltransferases; D011503:Transglutaminases; D006854:Hydrocortisone