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 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.
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Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque 87131, USA. dkusewitt@salud.unm.edu
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D000818:Animals; D003316:Corneal Diseases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000528:radiation effects*; D011905:Genes, ras / Q000528:radiation effects*; D008027:Light; D008297:Male; D016296:Mutagenesis / Q000528:radiation effects*; D009893:Opossums; D017354:Point Mutation / Q000528:radiation effects; D012513:Sarcoma, Experimental / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014466:Ultraviolet Rays