LOW-DOSE ULTRAVIOLET EXPOSURE EARLY IN DEVELOPMENT CAN LEAD TO WIDESPREAD MELANOMA IN THE OPOSSUM MODEL

Suckling young of opossums (Monodelphis domestica) were exposed to ult raviolet radiation (UVR, predominantly UVB: 290-320 nm) in part to det ermine an optimal protocol for induction and progression of melanoma i n this species. In all, 620 litters were introduced to one of seven pr otocols. The lowest dose (175 J/m(2)) administered three times a week for almost three weeks led to the highest incidence of melanotic lesio ns with melanoma potential (8.1%) among young (5-month-old) adults. Am ong 101 much older animals (>17 months at necropsy), 43% showed metast atic melanoma to the lymph nodes and almost one-third of these had pro gressed to widespread dissemination. Three of the latter animals, from a total of 13 obtained so far, were selected for detailed histologica l examination of disseminated disease. At necropsy, all three showed w idespread metastases beyond the lymph nodes to the spleen, lungs, and other distant sites. Histological changes typical of malignant melanom a included junctional activity, mitotic figures, and nerve and vessel invasion. This novel finding leads us to conclude that UVR can act as a complete carcinogen for progression to widely disseminated disease a nd that exposure of sucklings can lead, in old age, to widespread meta static melanoma in this model. The results are thus not inconsistent w ith the view that, in humans, early exposure to sunlight might act as an initiating factor in a later progression to malignant melanoma.