Prolonged and repeated exposure of the skin to ultraviolet light (UV) leads not only to aging of the skin but also increases the incidence of non-melanoma skin cancer (NMSC). Damage of cells induced by ultraviolet B (UVB) light both at the DNA level and molecular level initiates the activation of transcription factor pathways, which in turn regulate the expression of a number of genes termed the "UV response genes". Two such transcription factor families that are activated in this way are those of the nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) families. These two transcription factor families have been identified to be involved in the processes of cell proliferation, cell differentiation and cell survival and therefore play important roles in tumorigenesis. The study of these two transcription factor pathways and the cross-talk between them in response to UVB exposure may help with the development of new chemopreventive strategies for the prevention of UVB-induced skin carcinogenesis.

Secreted phosphoprotein I (SPP), also known as 2ar, osteopontin, 44-kDa bone phosphoprotein, bone sialoprotein I, and transformation-related phosphoprotein, is a 41.5-kDa glycosylated phosphoprotein secreted by many mammalian cell lines and expressed in a limited set of tissues. Using a cDNA probe, we found that SPP mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderate-to-high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous-cell carcinomas induced by an initiation-promotion regimen. This contrasts with the transient induction we had previously observed after a single application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In a set of 5 independently isolated T24-H-ras-transfected mouse C3H 10T1/2 cell lines, the levels of SPP mRNA correlated well with ras mRNA levels and with both experimental and spontaneous metastatic ability. SPP mRNA expression was also elevated in a derivative of mouse LTA cells transfected with genomic DNA from B16F1 melanoma cells and selected for increased experimental metastatic ability in the chick embryo. This apparent association of SPP expression with invasion, progression and metastasis, along with the presence of a functional ArgGlyAsp (RGD) cell adhesion site in SPP (osteopontin), leads us to propose that SPP may act as an autocrine adhesion factor for tumor cells.

The recent discovery that fullerenes (C60) can be produced in macroscopic quantities has sparked much interest in the chemistry of this unusual molecule. Concerns have also arose about the potential carcinogenic effects of this molecule. We have addressed the potential acute and subchronic toxic effects of fullerenes applied in benzene on the mouse skin. The acute toxic effects measured in this study included epidermal DNA synthesis and the induction of ornithine decarboxylase activity in the epidermis. At the topical dose of fullerenes used in these studies (i.e., 200 ug), we found no effect on either DNA synthesis or ornithine decarboxylase activity over a 72 hour time course after treatment. The subchronic effects of the fullerenes as a mouse skin tumor promoter was assessed by repeatedly applying the chemical to the skin after initiation with the polycyclic aromatic hydrocarbon, 7,12-dimethlybenz-anthracene (DMBA). Repeated administration of the fullerenes for up to 24 weeks post-initiation did not result in either benign or malignant skin tumor formation, whereas promotion with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the formation of benign skin tumors. Our data indicate that fullerenes applied in benzene at a likely industrial exposure level do not cause acute toxic effects on the mouse skin epidermis.

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