Genetic Analysis of Susceptibility to Spontaneous and UV-Induced Carcinogenesis in Xiphophorus Hybrid Fish

Rs, Nairn; Kazianis, Steven; L, Della Coletta; Trono, David; Ap, Butler; Rb, Walter; Dc, Morizot

doi:10.1007/s1012601-0004-7

Cited by 37 publications

(31 citation statements)

References 58 publications

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“…should also be noted that the degree of pigmentation in these BC 1 hybrids is genetically regulated (13). We believe the relationship between pigmentation and melanomagenesis is not linear because it appears that a threshold level of pigmentation (i.e., melanocytes, macromelanophores, and melanin) is necessary for tumorigenesis in Xiphophorus.…”

Section: Degree Of Adult Pigmentation Was Positively Correlated With Thementioning

confidence: 86%

“…The classical, spontaneous Xiphophorus hybrid melanoma model has been studied for over 80 years and offers powerful genetic and biochemical approaches for revealing determinants of melanomagenesis (12)(13)(14). The Xiphophorus melanoma receptor kinase gene (XMRK) behaves as a dominant oncogene in this fish model and is a mutated derivative of the fish ortholog for the human epidermal growth factor receptor (EGFR/ErbB-1).…”

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confidence: 99%

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Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Mitchell

Fernandez

Nairn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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We examined the wavelength dependence of ultraviolet (UV) radiation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.ultraviolet B | DNA damage | cyclobutane dimer | reactive oxygen species | melanin I n the late 1980s Setlow and coworkers used genetic hybrids from interspecific crosses involving several species of the fish genus Xiphophorus to investigate the effects of UVR on the induction of cutaneous malignant melanoma (CMM) (1). These pioneering studies demonstrated that ultraviolet B (UVB) irradiation of backcross hybrids generated from a specific genetic crossing scheme induced melanomas at significant frequencies above spontaneous levels. These results were later confirmed, and the genetic basis of UVB-induced melanoma susceptibility in this cross was recognized to be the same as in the well-studied spontaneous Xiphophorus hybrid melanoma model (2). In 1993, Setlow used a different Xiphophorus interspecies cross (designated as Sp-couchianus; Fig. 1) to study the wavelength dependence of melanoma induction and reported that wavelengths in the ultraviolet A (UVA) and visible ranges were effective in inducing melanomas in first-generation backcross (BC 1 ) hybrids generated from this particular cross (3). An action spectrum for melanoma induction was proposed with maxima in the UVB (302/313 nm) and UVA (365 nm) ranges. Because UVA fluence is quantitatively much greater than UVB in sunlight incident to the earth's surface (∼10-fold), Setlow suggested that, on the basis of this action spectrum, UVA was more effective than UVB in causing melanomas in the human population (2, 4). This report had significant public health consequences; it suggested that the use of commercially available sunscreens that effectively blocked UVB but not UVA encouraged more lengthy recreational sunlight exposure and thereby increased the exposure to UVA and its associated risks. Over the past 20 years, these data have become central to the debate on the role of UVA in melanoma and the risks associated with recreational and artificial exposures to UVA wavelengths.Debate over the action spectrum for melanoma has only intensified because subsequent r...

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Section: Degree Of Adult Pigmentation Was Positively Correlated With Thementioning

confidence: 86%

mentioning

confidence: 99%

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Mitchell

Fernandez

Nairn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…(10) Many interspecific crosses (and exceptionally even intraspecific crosses) have been described resulting in the development of conspicuous hyperpigmentation, which predisposes to mutagen-induced or UV-induced tumors, or to spontaneous formation of malignant melanoma. (11,12) The classical crossing experiment for spontaneous melanomagenesis is shown in Fig. 1.…”

Section: Tumor Formation In Xiphophorus Fishmentioning

confidence: 99%

Evolution of Xmrk: an oncogene, but also a speciation gene?

Schartl

2008

BioEssays

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Genes that exert their function when they are introduced into a foreign genetic background pose many questions to our current understanding of the forces and mechanisms that promote either the maintenance or divergence of gene functions over evolutionary time. The melanoma inducing Xmrk oncogene of the Southern platyfish (Xiphophorus maculatus) is a stable constituent of the genome of this species. It displays its tumorigenic function, however, almost exclusively only after inter-populational or, even more severely, interspecific hybridization events. The Xiphophorus hybrid melanoma system has gained attention in biomedical research as a genetic model for studying tumor formation. From an evolutionary perspective, a prominent question is: how could this gene persist over millions of years? An attractive hypothesis is that Xmrk, acting as a detrimental gene in a hybrid genome, could be a speciation gene that shields the gene pool of its species from mixing with other closely related sympatric species. In this article, I briefly review our current knowledge of the molecular genetics and biochemical functions of the Xmrk gene and discuss aspects of its evolutionary history and presence with respect to this idea. While Xmrk as a potentially injurious oncogene has clearly survived for millions of years, its role as a speciation gene has to be questioned.

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“…Widely differing Xiphophorus hybrid crosses have been utilized for the study of spontaneous, chemically-and physically-induced tumorigenesis, 4 as well as the study of sex determination, 32 and sexual maturation. 37 In several Continued D of these cases, substantial linkage mapping has been used within such hybrid crossing schemes for the purposes of localizing disease loci (reviewed by Naim et al 4 ).…”

Section: Overall Marker Availability In Xiphophorusmentioning

confidence: 99%

“…37 In several Continued D of these cases, substantial linkage mapping has been used within such hybrid crossing schemes for the purposes of localizing disease loci (reviewed by Naim et al 4 ). In addition, microsatellite loci have recently been developed and used in mapping studies in a cross between X. maculatus (Jp 163 B) and X. andersi.…”

Section: Overall Marker Availability In Xiphophorusmentioning

confidence: 99%

The Genetic Map ofXiphophorusFishes Represented by 24 Multipoint Linkage Groups

et al. 2004

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Hybrids between distinct Xiphophorus species have been utilized for over 70 years to study melanoma and other neoplasms that can develop spontaneously in hybrid offspring. Genetic linkage mapping has proven to be important in delineating genomic areas that harbor oncogenes and tumor suppressors. Within this report, two parallel backcrosses have been utilized to generate a genetic linkage map for Xiphophorus fishes. Isozyme/allozyme, RFLP and PCR-based mapping techniques, including AP-PCR/RAPDs and microsatellite loci were utilized. The derived linkage map provides a total of 403 mapped polymorphisms distributed among 24 linkage groups, representative of 24 acro- and telocentric chromosome pairs. Genomic coverage is approximately one marker per 5.8 cM. Detailed genotypic analysis of the utilized hybrids revealed two areas of the genome that show significant segregation distortion. Loci within the linkage group harboring the sex determining locus (LG 24) and an autosomal linkage group (LG 21) show highly significant deviations from Mendelian expectations. This phenomenon is not present in a hybrid cross that utilizes a different backcross hybrid progenitor species. The derived map with sequence-tagged markers provides a framework for physical map generation, large-scale genomic sequencing and will further enable cross-genome comparisons of vertebrate genomes.

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Genetic Analysis of Susceptibility to Spontaneous and UV-Induced Carcinogenesis in Xiphophorus Hybrid Fish

Cited by 37 publications

References 58 publications

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

Evolution of Xmrk: an oncogene, but also a speciation gene?

The Genetic Map ofXiphophorusFishes Represented by 24 Multipoint Linkage Groups

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