title: Enhanced sensitivity of the RET proto-oncogene to ionizing radiation in vitro.
abstract: Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia and thyroid cancer. It has been known for a long time that exposure of cells to radiation results in extensive DNA damage; however, a small number of studies have tried to explain the mechanisms of radiation-induced carcinogenesis. The high prevalence of RET/PTC rearrangements in patients who have received external radiation, and the evidence of in vitro induction of RET rearrangements in human cells, suggest an enhanced sensitivity of the RET genomic region to damage by ionizing radiation. To assess whether RET is indeed more sensitive to radiations than other genomic regions, we used a COMET assay coupled with fluorescence in situ hybridization, which allows the measurement of DNA fragmentation in defined genomic regions of single cells. We compared the initial DNA damage of the genomic regions of RET, CXCL12/SDF1, ABL, MYC, PLA2G2A, p53, and JAK2 induced by ionizing radiation in both a lymphoblastoid and a fetal thyroid cell line. In both cell lines, RET fragmentation was significantly higher than in other genomic regions. Moreover, a differential distribution of signals within the COMET was associated with a higher percentage of RET fragments in the tail. RET was more susceptible to fragmentation in the thyroid-derived cells than in lymphoblasts. This enhanced susceptibility of RET to ionizing radiation suggests the possibility of using it as a radiation exposure marker.
authors.affiliation: Institute of Genetic Medicine, European Academy, Bolzano, Italy.
authors.forename: Claudia Béu
authors.initials: CB
authors.lastname: Volpato
authors.forename: Minerva
authors.initials: M
authors.lastname: Martínez-Alfaro
authors.forename: Raffaella
authors.initials: R
authors.lastname: Corvi
authors.forename: Coralie
authors.initials: C
authors.lastname: Gabus
authors.forename: Sylvie
authors.initials: S
authors.lastname: Sauvaigo
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Elena
authors.initials: E
authors.lastname: Bonora
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Grandi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romeo
mesh_terms: D002460:Cell Line; D020552:Comet Assay; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007953:Leukemia, Radiation-Induced / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011839:Radiation, Ionizing; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret