High Relative Biologic Effectiveness of Carbon Ion Radiation on Induction of Rat Mammary Carcinoma and its Lack of H-ras and Tp53 Mutations

Journal Article · Sat Sep 01 04:00:00 EDT 2007 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2007.05.026· OSTI ID:21036216

Imaoka, Tatsuhiko ^[1]; Nishimura, Mayumi; Kakinuma, Shizuko; Hatano, Yukiko; Ohmachi, Yasushi ^[1]; Yoshinaga, Shinji Ph.D. ^[2]; Kawano, Akihiro ^[3]; Maekawa, Akihiko ^[4]; Shimada, Yoshiya ^[1]

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1. Experimental Radiobiology for Children's Health Research Group, Chiba (Japan)
2. Regulatory Sciences Research Group, National Institute of Radiological Sciences, Chiba (Japan)
3. Department of Technical Support and Development, National Institute of Radiological Sciences, Chiba (Japan)
4. Chemical Management Center, National Institute of Technology and Evaluation, Tokyo (Japan)

Purpose: The high relative biologic effectiveness (RBE) of high-linear energy transfer (LET) heavy-ion radiation has enabled powerful radiotherapy. The potential risk of later onset of secondary cancers, however, has not been adequately studied. We undertook the present study to clarify the RBE of therapeutic carbon ion radiation and molecular changes that occur in the rat mammary cancer model. Methods and Materials: We observed 7-8-week-old rats (ACI, F344, Wistar, and Sprague-Dawley) until 1 year of age after irradiation (0.05-2 Gy) with either 290 MeV/u carbon ions with a spread out Bragg peak (LET 40-90 keV/{mu}m) generated from the Heavy-Ion Medical Accelerator in Chiba or {sup 137}Cs {gamma}-rays. Results: Carbon ions significantly induced mammary carcinomas in Sprague-Dawley rats but less so in other strains. The dose-effect relationship for carcinoma incidence in the Sprague-Dawley rats was concave downward, providing an RBE of 2 at a typical therapeutic dose per fraction. In contrast, {approx}10 should be considered for radiation protection at low doses. Immunohistochemically, 14 of 18 carcinomas were positive for estrogen receptor {alpha}. All carcinomas examined were free of common H-ras and Tp53 mutations. Importantly, lung metastasis (7%) was characteristic of carbon ion-irradiated rats. Conclusions: We found clear genetic variability in the susceptibility to carbon ion-induced mammary carcinomas. The high RBE for carbon ion radiation further supports the importance of precise dose localization in radiotherapy. Common point mutations in H-ras and Tp53 were not involved in carbon ion induction of rat mammary carcinomas.

• OSTI ID: 21036216
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 69; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BRAGG CURVE
CARBON IONS
CARCINOGENESIS
CARCINOMAS
CESIUM 137
ESTROGENS
GAMMA RADIATION
GENE MUTATIONS
GENETIC VARIABILITY
HEAVY IONS
IRRADIATION
LET
LUNGS
METASTASES
RADIATION DOSES
RADIATION PROTECTION
RADIOTHERAPY
RATS
RBE
RECEPTORS