Photoreactivation does not alter ras and p53 mutation spectra in ultraviolet radiation-induced corneal sarcomas of Monodelphis domestica

When chronically exposed to ultraviolet radiation (UV), opossums of the spe cies Monodelphis domestica develop corneal sarcomas at high frequency. Post -UV exposure to photoreactivating light enhances repair of UV-induced pyrim idine dimers and suppresses, but does not abrogate, corneal tumor developme nt. 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 typ es of mutation suppressed by enhanced repair of pyrimidine dimers. Mutation s were detected by polymerase chain reaction amplification followed by dire ct sequencing or by "cold" single-strand conformational polymorphism analys is. The overall frequency of mutations was low, and there was no statistica lly significant difference between the two groups of tumors in the frequenc y or type of mutation. All mutations occurred at dipyrimidine sites, and mo st were C to T or CC to TT mutations, the hallmark UV-induced mutations. Ho tspots of p53 mutation identified in a previous study of invasive tumors we re absent, and mutations identified in the present study included synonymou s 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 proxima te carcinogen for these tumors. The low incidence of mutations suggest that neither ras activation nor p53 inactivation is essential for tumor formati on. Mutations attributable specifically to pyrimidine dimer formation could not be identified. (C) 2000 Wiley-Liss, Inc.