Tumor aggressiveness is independent of radiation quality in murine hepatocellular carcinoma and mammary tumor models

Purpose. Estimating the cancer risk associated with interplanetary travel is complicated by the lack of data for human exposure to high atomic number, high-energy (HZE) radiation encountered in space. Therefore, human exposure data from low linear energy transfer (low-LET) γ-ray radiation is used in cancer risk models with the critical assumption that HZE and γ-ray radiation have comparable biological effects, including the induction of the same spectrum of tumors with similar lethality. Recently this assumption has been challenged by several reports indicating that HZE radiation might produce more aggressive tumors. The goal of this research is to test the hypothesis that high-LET HZE radiation induced tumors are more aggressive than those that arise spontaneously or from exposure to low-LET γ-rays. Materials & methods. The FVB/N-Tg(MMTV-PyMT) and (DBAxFVB)F1-Tg(MMTV-PyMT) murine models of mammary cancer and the C3H-Tg(Afp-mCherry) and C3B6F1-Tg(Afp-mCherry) liver cancer models were used to determine the impact of exposure to 0.2 Gy of HZE 300 MeV/n silicon ions in comparison to 3 Gy of γ-rays and no radiation. Various measures of tumor aggressiveness including latency, size, pathological grade, prognostic biomarkers, metastasis, and survival were assessed. Results. For both mammary cancer models, there was no significant change in the latency of mammary tumors or in the number or size of pulmonary metastasis in silicon-irradiated mice compared to their sham-irradiated controls. For the C3H-Tg and C3B6-Tg liver cancer models, we did observe an increase in the incidence of liver cancer in irradiated mice, but no differences in measures of aggressiveness, including tumor size, grade, metastasis, or overall survival. Conclusion. The principle finding of our study is that tumors in the HZE-irradiated mice were not more aggressive than those arising from exposure to low-LET γ-rays or spontaneously. Thus, we conclude that enhanced aggressiveness does not appear to be a uniform characteristic of all tumors in HZE-irradiated animals.