NONMAMMALIAN MODELS FOR SUNLIGHT CARCINOGENESIS - GENETIC-ANALYSIS OFMELANOMA FORMATION IN XIPHOPHORUS HYBRID FISH

Genetic hybrids of Xiphophorus fishes have been used for decades to st udy heritable melanoma formation. In these models, overexpression of p igmentation patterns from melanin-producing pigment cells can lead to genetically regulated melanoma formation in backcross hybrids, In the best studied of these models, the Gordon-Kosswig hybrid melanoma, tumo rs form spontaneously in all individuals of a subset of backcross hybr ids between the platyfish Xiphophorus maculatus Jp 163 A and the sword tail species Xiphophorus helleri. Backcross hybrids susceptible to mel anoma formation inherit a sea-linked oncogene, Xmrk, associated with t he spotted dorsal (Sd) pigment pattern and have lost both copies of an autosomal gene, DIFF, from the X. maculatus parent, Spontaneous melan oma formation conforms to simple, two-gene Mendelian inheritance in wh ich DIFF behaves as a recessive tumor suppressor gene, Recently, Xipho phorus hybrids in which melanomas can be induced by UV and near-UV vis ible light exposure have been described, We report here results of gen etic linkage analysis of one of these Xiphophorus light-inducible hybr id melanoma models, in backcross hybrids between the two platyfish spe cies X, maculatus Jp 163 B and Xiphophorus; couchianus. Our linkage re sults provide the first estimate of recombination between the tumor su ppressor locus, DIFF, and glycerate-2-dehydrogenase (GLYDH) in Xiphoph orus linkage group V. Also, they demonstrate that DIFF regulates hyper plasia of spotted side (Sp) pigment cells in this hybrid model, analog ous to its regulation of hyperplasia of Sd pigment cells in the ''clas sical'' Gordon-Kosswig hybrid. Joint segregation analyses of melanoma- bearing fish indicate that segregation of DIFF is genetically linked t o melanoma induction by 405 nm light in this model but that induction of melanomas by UV wavelengths apparently does not depend on segregati on of the DIFF locus.