title: Effects of selenomethionine in irradiated human thyroid epithelial cells and tumorigenicity studies.
abstract: The objectives of the present study were to characterize γ-ray, 1 GeV/n proton, and 1 GeV/n iron ion radiation-induced adverse biological effects in terms of toxicity and transformation of HTori-3 human thyroid epithelial cells; to evaluate the ability of L-selenomethionine (SeM) to protect against radiation-induced transformation when present at different times during the assay period; and to evaluate the tumorigenicity of HTori-3 cells derived from anchorage-independent colonies following iron ion radiation exposure. Cell survival was determined by a clonogenic assay, transformation was measured by a soft agar colony formation assay, and the tumorigenic potential of the cells was determined by injecting them subcutaneously into athymic nude mice and monitoring tumor formation. The results demonstrate that exposure of HTori-3 cells to γ-ray, proton, or iron ion radiation resulted in decreased clonogenic survival, which persisted for weeks after the radiation exposure. Treatment with SeM initiated up to 7 days after the radiation exposure conferred significant protection against radiation-induced anchorage-independent growth. HTori-3 cells derived from all evaluated anchorage-independent colonies formed tumors when injected into athymic nude mice, indicating that these cells are tumorigenic and that anchorage-independent colony growth is a reliable surrogate endpoint biomarker for the radiation-induced malignant transformation of HTori-3 cells.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ware
authors.forename: Zhaozong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ana L
authors.initials: AL
authors.lastname: Romero-Weaver
authors.forename: X Steven
authors.initials: XS
authors.lastname: Wan
authors.forename: Paul M
authors.initials: PM
authors.lastname: Newberne
authors.forename: Ann R
authors.initials: AR
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D007501:Iron / Q000009:adverse effects; D051379:Mice; D008819:Mice, Nude; D017711:Nonlinear Dynamics; D011522:Protons / Q000009:adverse effects; D012044:Regression Analysis; D012645:Selenomethionine / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D011522:Protons; D012645:Selenomethionine; D007501:Iron