Abstract
Improvement in the survival of patients treated with heavy ion therapy may in turn raise a concern about secondary cancer risk. We conducted a series of animal experiments to investigate the carcinogenic effect of carbon ions from the HIMAC synchrotron at NIRS on mammary gland, one of the most susceptible organs to radiation carcinogenesis. First, we compared the susceptibility of four rat strains to mammary cancer induction by the carbon ion SOBP beam and found that only Sprague-Dawley rats showed significantly increased cancer incidence. Using this strain, we next clarified that the dose-effect relationship for carbon ions (0.05–2 Gy) was convex upward, whereas that for 137Cs γ-rays (0.5–2 Gy) was linear, resulting in a dose-dependent relative biologic effectiveness that ranged from 10 to 2 at doses 0.05–1 Gy. Lung metastasis was prominent in carbon ion-irradiated rats. Primary tumors were mostly (~80%) positive for estrogen receptor but lacked H-ras and Tp53 mutations. Using microarrays, we compared the gene expression profiles and genomic copy number changes between carbon ion- and γ-ray-induced cancers; however, we did not observe a marked difference. On the other hand, irradiation of carbon ion mono beam at 1 Gy did not result in significant cancer induction. These results suggest that the carcinogenic effect of carbon ions varies depending on the genetic background and is strong in the SOBP region. Our current data indicate no remarkable molecular and biological difference between carbon ion- and γ-ray-induced mammary cancers except for the metastatic ability.
