Sub-lethal Cellular response of human normal cells along the Bragg curve for different ion beams: implications for human health and charged particle radiobiology

Charged particles are adopted for cancer hadrontherapy and account for environmentally relevant exposures (indoor radon, Space radiation). Assessment of therapy late effects and risk estimates fall short of accuracy. Exposure of astronauts to HZE radiation and of patients to ion beams share radiobiological effects and common uncertainties. These are twofold: Lack of experimental data on sublethal long-term biological effects, relevant for tissue morbidity; inadequacy of models based on dose and LET, which disregard ion-track structure, the key property that drives radiation quality effectiveness. Cellular response to radiation is governed by highly inhomogeneous clusters and ionisation varieties within and around tracks, activating sensing/signaling pathways. Track diameter is proportional to LET but depends on energy and, for a given energy, on particle Z, hence ionisation patterns vary between same-LET ions. Thus, ion effectiveness may depend on particle Z and vary with penetration depth. “Biological” Bragg curves mirroring physical ones may then improve understanding of ion radiobiology. Despite improved dose-shaping contours and tissue sparing, secondary cancers are of concern in hadrontherapy (e.g. in paediatric cases). Non-cancer late effects also determine treatment outcome and may affect Space crews. Cancer and non-cancer late effects originate from cells that survived the initial insult. Sublethal damage data from positions along Bragg curves will be discussed. Normal human cells (HUVEC and MCF-10A) were irradiated with 290 MeV/u or 14 MeV 12C, 60/u MeV 16O and 20Ne (0.1-2.5 Gy), using SIS accelerator, Darmstadt, Germany; LNS-INFN cyclotron, Catania, Italy; TTT-3 Tandem, Federico II Naples University, Italy. Stress-Induced Premature Senescence (SIPS) and chromosome aberrations (CAs) were studied by-galactosidase assay and FISH staining of chemically-induced PCCs, respectively. In vivo accumulation of ectopically senescing cells may disrupt tissue homeostasis. Further, cells undergoing SIPS reportedly secrete factors inhibiting or promoting tumour proliferation (Senescence–Associated Secretory Phenotype). A well-known cancer biomarker, CAs may lead to genomic instability and transformation. Results show that cytogenetic damage does vary along ion path and, for similar LETs, between ion species. Hence, Monte-Carlo codes ought to incorporate track-structure features and sublethal biological data in modeling cellular response to charged particles.