Photocarcinogenesis in Human Adult Skin Grafts

It has been demonstrated previously that the exposure to 7,12-dimethyl[a]benzanthracene (DMBA) and UVB radiation leads to the development of epidermal cysts, squamous cell carcinomas (SCC), melanocytic hyperplasia and melanoma in human foreskins from newborns grafted to immunodeficient mice. Improved techniques in grafting full-thickness skin from adults have enabled us to study photocarcinogenesis in human skin from different body sites and from older donors. One hundred and fifty-five normal white skin specimens from the trunk and face of 53 adult individuals were grafted onto severe combined immunodeficient (SCID) and recombinase activating gene-1 (Rag-1) knockout mice and irradiated two to three times weekly with 40 mJ/cm(2) UVB or solar-simulated UV (SSUV) over a period of up to 10 months with or without one prior topical application of DMBA. Over an observation period of 2-22 months, histopathological and immunohistochemical analyses of 134 specimens revealed actinic keratoses in 30% of the DMBA- + UV-treated grafts, in 18% of the grafts exposed to SSUV only, and in 10% of the grafts exposed to UVB only. Actinic keratoses were absent in grafts treated with DMBA only. One SCC was found in an abdominal skin graft 3 months after exposure to DMBA followed by UVB. Point mutations in codon 61 of the human Ha-ras gene were detected in the SCC, five of six analyzed actinic keratoses and in non-lesional epidermis of DMBA- and UVB-treated grafts, indicating that DMBA as well as UVB alone can induce these mutations in human skin. In contrast to the previous experience with neonatal foreskin grafts, melanocytic lesions were not found except for mild hyperplasia in few cases. The data suggest that melanocytes from young individuals are more susceptible to the transforming effects of genotoxic agents than melanocytes from adults.