Resolution of UV-induced DNA damage in Xiphophorus fishes

The genus Xiphophorus is an important model for investigating the etiology and genetics of sunlight-induced melanoma as well as other cancers. We inve stigated the role DNA damage plays in tumorigenesis in Xiphophorus using a variety of immunological techniques to examine the induction, distribution, and repair of the major photoproducts in DNA after exposure to solar (ultr aviolet-B) radiation. We found that cyclobutane pyrimidine dimers (CPDs) we re induced at 5- to 10-fold greater frequency than the (6-4) photoproduct ( (6-4)PD) in Xiphophorus signum, and the efficiency of photoproduct formatio n was tissue-dependent, with the scales providing considerable photoprotect ion against both types of damage. Both of these lesions are efficiently rep aired in the presence of visible light by photoenzymatic repair with CPDs r epaired at about twice the rate of (6-4)PDs. Photoenzymatic repair of cyclo butane dimers is inducible by prior exposure to low levels of visible light and can be extremely rapid, with most of the lesions removed within 30 min utes. In the absence of light, dimers are removed by nucleotide excision re pair with somewhat greater efficiency for the (6-4)PD compared with the CPD in most species. The relative efficiencies of nucleotide excision repair a nd photoenzymatic repair are tissue-specific and species-specific. The dive rse photochemical and photobiological responses observed in Xiphophorus fis hes suggest that heritable traits governing the induction and repair of DNA damage may be involved in the susceptibility of Xiphophorus hybrids to mel anomagenesis.