Heavy ion-induced mammary carcinogenesis

To evaluate the potential mammary carcinogenicity of 290-MeV/u carbon-ion 6-cm-spread-out Bragg peak (SOBP) beam, we sought for susceptible rat strains, investigated the dose-effect relationship between 0.05 and 2 Gy and analyzed expression of estrogen receptor α (ERα) and mutations of TP53 and H-ras genes. The carbon ions were carcinogenic to Sprague-Dawley and, to a lesser extent, Wistar rats but not to ACI/N or F344 strains. The dose-effect relationship was convex upward at doses less than 0.5 Gy, with a plateau up to 2 Gy. An estimated relative biological effectiveness (RBE) for palpable tumor induction was 4-7 at low doses. Induced tumors were immunohistochemically positive for ERα and negative for TP53 mutation, resembling rat mammary tumors induced by chemical carcinogens. Moreover, all induced tumors were negative for H-ras mutations, unlike chemically-induced tumors, but similar to spontaneous and γ-ray-induced tumors. These results suggest that 290-MeV/u carbon-ion 6-cm-SOBP beam may result in an increased risk of secondary cancer. (author)