Enhanced sensitivity of the RET proto-oncogene to ionizing radiation in vitro.
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.
Volpato
Claudia Béu
CB
Institute of Genetic Medicine, European Academy, Bolzano, Italy.
Martínez-Alfaro
Minerva
M
Corvi
Raffaella
R
Gabus
Coralie
C
Sauvaigo
Sylvie
S
Ferrari
Pietro
P
Bonora
Elena
E
De Grandi
Alessandro
A
Romeo
Giovanni
G
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
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret