When chronically exposed to ultraviolet radiation (UV), opossums of the species Monodelphis domestica develop corneal
sarcomas at high frequency. Post-UV exposure to photoreactivating light enhances repair of UV-induced
pyrimidine dimers and suppresses, but does not abrogate, corneal
tumor development. We compared mutation spectra in ras and p53 genes in 32 eye
tumors from Monodelphis exposed to UV alone and in 25
tumors from Monodelphis exposed to UV followed by photoreactivation in order to identify the particular types of mutation suppressed by enhanced repair of
pyrimidine dimers. Mutations were detected by polymerase chain reaction amplification followed by direct sequencing or by "cold" single-strand conformational polymorphism analysis. The overall frequency of mutations was low, and there was no statistically significant difference between the two groups of
tumors in the frequency or type of mutation. All mutations occurred at dipyrimidine sites, and most were C to T or CC to TT mutations, the hallmark UV-induced mutations. Hotspots of p53 mutation identified in a previous study of invasive
tumors were absent, and mutations identified in the present study included synonymous mutations not previously detected. The difference in stage of the
tumors examined is believed to account for these differences. The preponderance of signature UV mutations in p53 and ras genes confirm that UV is the proximate
carcinogen for these
tumors. The low incidence of mutations suggest that neither ras activation nor p53 inactivation is essential for
tumor formation. Mutations attributable specifically to
pyrimidine dimer formation could not be identified.