Response of murine epidermal keratinocyte cultures to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD): Comparison of haired and hairless genotypes

Abstract

Based on the observation that congenic haired and hairless mice differ in the hyperkeratinizing/hyperproliferative epidermal response following topical exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in vivo, it has been proposed that this response in mice segregates with the Ah locus (which controls for the Ah receptors) and the hr locus (for hairlessness) ( Knutson and Poland, 1982). In the present studies this hypothesis was tested by comparing the response of epidermal keratinocytes derived from genotypically segregated newborn haired and hairless HRS J mice to TCDD exposure in in vitro cultures. The parameters monitored were stimulation of cell proliferation (as measured by protein content and rate of tritiated thymidine incorporation in cultures), epidermal transglutaminase activity, cornified cell envelope formation, and keratin staining with Rhodanile blue. Results suggested that the sensitivity of HRS J haired and hairless mouse epidermal keratinocyte cultures to TCDD exposure in vitro was very similar. In both cell cultures all parameters monitored were stimulated by TCDD exposure in a similar dose-dependent manner. This suggests that physiologic factors beyond the epidermal cells may be involved in expression of the different responses seen in the skin of mice to TCDD in vivo.