This Program Project is an integrated effort focused on the development and use of unique animal tumor models represented by Xiphophorus interspecies hybrids, and is designed to investigate the molecular and genetic basis of tumor susceptibility. The Program is constituted of three Research Projects and two Cores. Project 1 will intensively investigate the role of ultraviolet (UV) radiation in melanoma formation, determining UV action spectra for melanomagenesis and for the induction and repair of UV-induced DNA damage in Xiphophorus tissues, tumors and cell lines. A particular focus will be the roles of a dominant oncogene (Xmrk) and tumor suppressor genes (CDKN2K, p53) in melanoma. Project 2 will develop a new and promising Xiphophorus model for neuroblastoma, and will use the alkylating chemical carcinogen N-methyl-N-nitrososurea (MNU) for melanoma, fibrosarcoma, and neuroblastoma induction in Xiphophorus hybrids. Experiments conducted in Projects 1 and 2 will allow comparison of UV- and MNU-induced carcinogenesis in genetically diverse melanoma models. DNA damaged induced by alkylating carcinogens and DNA repair will be correlated to endpoints such as toxicity and tumorigenesis, using specific radioimmunoassays and biochemical approaches to investigate repair mechanisms. Project 3 is concerned with expansion of the Xiphophorus gene map, providing markers useful for locating potential tumor susceptibility loci in all 24 Linkage Groups (LGs) for each of the established and new Xiphosphous hybrid tumor models to be developed in these studies. In all Research Projects, genetic linkage analysis, coordinated through Project 3, will be used to identify and locate in the Xiphophorus gene map any loci associated with tumor susceptibility. Core A will provide administrative and research support to the Research Projects, including biostatistics and histopathology support. In addition, fiscal administration, organization of internal research group interactions will be implemented by Core A. Core B will supervise and maintain all fish stocks and strains, and perform hybridizations, production of tumor susceptible backcross hybrids, UV and MNU treatments, outgrowth, and dissections to provide materials for analysis to the individual projects. These integrate goals offer the prospect of addressing fundamental, broadly relevant scientific questions concerning the molecular and genetic basis of genetic susceptibility to tumorigenesis.
| 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 |
| Walter, Christi A; Intano, Gabriel W; McMahan, C Alex et al. (2004) Mutation spectral changes in spermatogenic cells obtained from old mice. DNA Repair (Amst) 3:495-504 |
| Walter, R B; Rains, J D; Russell, J E et al. (2004) A microsatellite genetic linkage map for Xiphophorus. Genetics 168:363-72 |
| 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 |
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