title: High Energy Particle Radiation-associated Oncogenic Transformation in Normal Mice: Insight into the Connection between Activation of Oncotargets and Oncogene Addiction.
abstract: Concerns on high-energy particle radiation-induced tumorigenic transformation of normal tissue in astronauts, and in cancer patients undergoing radiotherapy, emphasizes the significance of elucidating the mechanisms involved in radiogenic transformation processes. Mostly used genetically modified or tumor-prone models are less reliable in determining human health risk in space or protracted post-treatment normal tissue toxicity. Here, in wild type C57BL/6 mice, we related the deregulation of distinctive set of tissue-specific oncotargets in major organs upon56Fe (600 MeV/amu; 0.5 Gy/min; 0.8 Gy) particle radiation and compared the response with low LET γ-radiation (137Cs; 0.5 Gy/min; 2 Gy). One of the novel findings is the 'tissue-independent' activation of TAL2 upon high-energy radiation, and thus qualifies TAL2 as a potential biomarker for particle and other qualities of radiation. Heightened expression of TAL2 gene transcript, which sustained over four weeks post-irradiation foster the concept of oncogene addiction signaling in radiogenic transformation. The positive/negative expression of other selected oncotargets that expresses tissue-dependent manner indicated their role as a secondary driving force that addresses the diversity of tissue-dependent characteristics of tumorigenesis. This study, while reporting novel findings on radiogenic transformation of normal tissue when exposed to particle radiation, it also provides a platform for further investigation into different radiation quality, LET and dose/dose rate effect in healthy organs.
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Aravindan
authors.affiliation: Stephenson Cancer Center, Oklahoma City, OK, USA.
authors.forename: Sheeja
authors.initials: S
authors.lastname: Aravindan
authors.affiliation: Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Manickam
authors.affiliation: Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Mohan
authors.initials: M
authors.lastname: Natarajan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology / Q000528:radiation effects; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D020287:In Situ Nick-End Labeling; D007477:Ions; D053555:Keratin-5 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D048631:Micronucleus, Germline / Q000378:metabolism; D000074723:Oncogene Addiction; D009857:Oncogenes; D009928:Organ Specificity / Q000528:radiation effects; D011827:Radiation; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis; D059467:Transcriptome / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D007477:Ions; D053555:Keratin-5; D016159:Tumor Suppressor Protein p53