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 investigated 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 (ultraviolet-B) radiation. We found that cyclobutane pyrimidine dimers (CPDs) were induced at 5- to 10-fold greater frequency than the (6-4) photoproduct ((6-4)PD) in Xiphophorus signum, and the efficiency of photoproduct formation was tissue-dependent, with the scales providing considerable photoprotection against both types of damage. Both of these lesions are efficiently repaired in the presence of visible light by photoenzymatic repair with CPDs repaired at about twice the rate of (6-4)PDs. Photoenzymatic repair of cyclobutane 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 minutes. In the absence of light, dimers are removed by nucleotide excision repair with somewhat greater efficiency for the (6-4)PD compared with the CPD in most species. The relative efficiencies of nucleotide excision repair and photoenzymatic repair are tissue-specific and species-specific. The diverse photochemical and photobiological responses observed in Xiphophorus fishes suggest that heritable traits governing the induction and repair of DNA damage may be involved in the susceptibility of Xiphophorus hybrids to melanomagenesis.