Clones derived in vitro from a parent culture of murine malignant melanoma cells varied greatly in their ability to produce metastatic colonies in the lungs upon intravenous inoculation into syngeneic mice. This suggests that the parent tumor is heterogeneous and that highly metastatic tumor cell variants preexist in the parental population.

Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these Immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V enulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV Irradiation is an effective tool for restoring Immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage.Wavelengths of UV radiation in the middle, or UV-B (280-320 nm), range can impair a variety of immune responses in humans and laboratory animals both locally, within UVirradiated skin, and systemically, at distant sites (1). Exposure of mice to UV-B radiation interferes with the rejection of UV-induced skin cancers and the induction of delayed and contact hypersensitivity (DHS and CHS) responses initiated at unirradiated sites; these forms of immune suppression are associated with the induction of antigen-specific suppressor T lymphocytes (2). How UV-B radiation exerts its systemic, immunosuppressive effects is a question of considerable interest, both for understanding the regulatory pathways governing these immune responses and for assessing the potential effects of UV-B radiation on human health. The DHS response is particularly important in this regard because this T-lymphocyte-mediated immune reaction is responsible for protection against many chronic infectious diseases.Current experimental evidence implicates soluble substances derived from UV-irradiated keratinocytes as the probable mediators of UV-induced systemic suppression of DHS and CHS responses (3-5). However, the initial photobiological reaction responsible for triggering the cascade of events leading to activation of the suppressor pathway of the immune response remains controversial. Based on an in vivo action spectrum for systemic suppression of CHS in the mouse, it has been proposed that urocanic acid, a deamination product of histidine, present in the stratum corneum, is the photoreceptor for this form of UV-induce...

Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.