Heredity can be a strong predisposing factor in the development of cutaneous malignant melanoma (CMM), a deadly cancer which is increasing in incidence. Although UV radiation is generally believed to play a role in CMM, the role of excessive sunlight exposure in the etiology of melanoma is controversial. Ozone depletion, predicted to increase UVB radiation incident to the earth's surface, may increase the risk of CMM in the human population. However, UVA ration represents a much greater component of sunlight than increasing melanoma incidence in humans, it is crucial to develop and test hypotheses that correlate excessive sunlight exposure with genetic factors underlying melanoma susceptibility can be recognized and potentially isolated are necessary. In this project, the genetic diversity generated by the hybridization of different Xiphophorus species will be exploited to develop and analyze several new experimental melanoma models, with the goal of identifying genetic determinants of spontaneous and HIV-induced tumorigenesis. The investigation of UV-induced melanoma formation in Xiphophorus melanoma models will establish UV action spectra for melanomagenesis, and for UV-induced DNA damage and repair in Xiphophorus tissues and cell lines. Experiments to examine the roles of oncogenes (Xmrk) and tumor suppressor genes (CDKN2X, p53) in melanoma in these models will address hypothesis regarding whether Xmrk over-expression is a common feature of Xiphophorus melanomas. Several hypotheses address the roles of suppressor genes in these tumor models will be developed, including whether suppressor gene dysfunction is determined by methylation patterns, promoter differences, or structural alterations. These studies will contribute to an understanding of how dominant oncogenes and tumor suppressor genes contribute to tumorigenesis in the unique Xiphophorus models, but are also directly relevant to understanding melanoma formation in humans, because of the evidence implicating CDKN2 as a human melanoma susceptibility gene. Investigation of CDKN2X, p53, and DNA damage in these unique model organisms will advance our understanding of the molecular etiology of melanoma.
| Butler, Andrew P; Trono, David; Coletta, Luis Della et al. (2007) Regulation of CDKN2A/B and Retinoblastoma genes in Xiphophorus melanoma. Comp Biochem Physiol C Toxicol Pharmacol 145:145-55 |
| Oehlers, Leon P; Perez, Amy N; Walter, Ronald B (2005) Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of 4-sulfophenyl isothiocyanate-derivatized peptides on AnchorChip sample supports using the sodium-tolerant matrix 2,4,6-trihydroxyacetophenone and diammonium citrate. Rapid Commun Mass Spectrom 19:752-8 |
| Huang, Changjiang; Dong, Qiaoxiang; Tiersch, Terrence R (2004) Sperm cryopreservation of a live-bearing fish, the platyfish Xiphophorus couchianus. Theriogenology 62:971-89 |
| David, Wendi M; Mitchell, David L; Walter, Ronald B (2004) DNA repair in hybrid fish of the genus Xiphophorus. Comp Biochem Physiol C Toxicol Pharmacol 138:301-9 |
| Huang, Changjiang; Dong, Qiaoxiang; Walter, Ronald B et al. (2004) Sperm cryopreservation of green swordtail Xiphophorus helleri, a fish with internal fertilization. Cryobiology 48:295-308 |
| Kazianis, Steven; Khanolkar, Vandeeta A; Nairn, Rodney S et al. (2004) Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes. Comp Biochem Physiol C Toxicol Pharmacol 138:291-9 |
| Heater, Sheila J; Oehlers Jr, Leon P; Rains, J Douglas et al. (2004) DNA polymerase beta mRNA and protein expression in Xiphophorus fish. Comp Biochem Physiol C Toxicol Pharmacol 138:325-34 |
| Huang, Changjiang; Dong, Qiaoxiang; Walter, Ronald B et al. (2004) Initial studies on sperm cryopreservation of a live-bearing fish, the green swordtail Xiphophorus helleri. Theriogenology 62:179-94 |
| Mitchell, David L; Nairn, Rodney S; Johnston, Dennis A et al. (2004) Decreased levels of (6-4) photoproduct excision repair in hybrid fish of the genus Xiphophorus. Photochem Photobiol 79:447-52 |
| Oehlers Jr, Leon P; Heater, Sheila J; Rains, J Douglas et al. (2004) Gene structure, purification and characterization of DNA polymerase beta from Xiphophorus maculatus. Comp Biochem Physiol C Toxicol Pharmacol 138:311-24 |
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