title: High-energy particle-induced tumorigenesis throughout the gastrointestinal tract.
abstract: Epidemiological data reveals the gastrointestinal (GI) tract as one of the main sites for low-LET radiation-induced cancers. Importantly, the use of particle therapy is increasing, but cancer risk by high-LET particles is still poorly understood. This gap in our knowledge also remains a major limiting factor in planning long-term space missions. Therefore, assessing risks and identifying predisposing factors for carcinogenesis induced by particle radiation is crucial for both astronauts and cancer survivors. We have previously shown that exposure to relatively high doses of high-energy (56)Fe ions induced higher intestinal tumor frequency and grade in the small intestine of Apc(Min/+) mice than γ rays. However, due to the high number of spontaneous lesions (∼30) that develop in Apc(Min/+) animals, this Apc mutant model is not suitable to investigate effects of cumulative doses <1 Gy, which are relevant for risk assessment in astronauts and particle radiotherapy patients. However, Apc(1638N/+) mice develop a relatively small number of spontaneous lesions (∼3 per animal) in both small intestine and colon, and thus we propose a better model for studies on radiation-induced carcinogenesis. Here, we investigated model particle radiation increases tumor frequency and grade in the entire gastrointestinal tract (stomach and more distal intestine) after high- and low-radiation doses whether in the Apc(1638N/+). We have previously reported that an increase in small intestinal tumor multiplicity after exposure to γ rays was dependent on gender in Apc(1638N/+) mice, and here we investigated responses to particle radiation in the same model. Phenotypical and histopathological observations were accompanied by late changes in number and position of mitotic cells in intestinal crypts from animals exposed to different radiation types.
authors: a Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC.
authors: Daniela
authors: D
authors: Trani
authors: Scott A
authors: SA
authors: Nelson
authors: Bo-Hyun
authors: BH
authors: Moon
authors: Jan J
authors: JJ
authors: Swedlow
authors: Elizabeth M
authors: EM
authors: Williams
authors: Steven J
authors: SJ
authors: Strawn
authors: Paul L
authors: PL
authors: Appleton
authors: Bhaskar
authors: B
authors: Kallakury
authors: Inke
authors: I
authors: Näthke
authors: Albert J
authors: AJ
authors: Fornace
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology* / Q000528:radiation effects*; D007501:Iron / Q000009:adverse effects; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000528:radiation effects; D060787:Neoplasm Grading; D012727:Sex Characteristics; D047368:Tumor Burden / Q000528:radiation effects
chemical_list: D007501:Iron