RECONSTITUTED 3-DIMENSIONAL HUMAN SKIN, A NEW IN VITRO MODEL FOR SKIN CARCINOGENESIS STUDY.

EpiDerm (MatTek Co., MA) is a newly developed reconstituted human skin equivalent that exhibits human skin-like morphological and growth characteristics. It has been utilized to evaluate the cytotoxicity and irritant potential of various cosmetic and household products. In this study, we found that EpiDerm can also be used to evaluate the genotoxicity of carcinogenic agents at the molecular level. Following exposure to several carcinogenic agents induction of the accumulation of tumor suppressor p53 gene product and the protooncogene c-fos and DNA photoadducts were demonstrated using immunohistochemistry. Eight hours after topical application of 50ug of benzo(a)pyrene, strong positive immunostaining for BP-DNA adducts, c-fos and p53 proteins occurred. Eight hours after exposure to ultraviolet B (UVB) and 24 hours after UVA, c-fos and p53 protein accumulation was detected. 8-Methoxypsoralen (8-MOP) plus UVA also resulted in augmented expression of DNA adducts and c-fos and p53 proteins. It is of interest that 8-MOP alone without UVA produced no detectable adducts but did increase p53 protein in this system. These studies indicate that human skin equivalent can provide a convenient and cost effective alternative to animal testing for studies related to probing the mechanism of environmentally induced cancer in the skin.

8-Methoxypsoralen (8-MOP), Cancer, Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Cytotoxicity, Dermal irritancy, Dermal irritancy testing, Dermal irritation, EpiDerm, Morphology/Morphological, Oncogene, c-fos, Phototoxicity, Skin carcinogenesis, Skin irritancy, Skin irritation, Sun screens, Tumor suppressor gene, p53, UVA, UVB, Ultra-violet radiation (UV)