Determination of the Effective Local Lethal Function for the NanOx Model.

NanOx is a biophysical model recently developed in the context of hadrontherapy to predict the cell survival probability from ionizing radiation. It postulates that this may be factorized into two independent terms describing the cell response to two classes of biological events that occur in the sequence of an irradiation: the local lethal events that occur at nanometric scale and can by themselves induce cell death, and the non-local lethal events that lead to cell death by an effect of accumulation and/or interaction at a larger scale. Here we address how local lethal events are modeled in terms of the inactivation of undifferentiated nanometric targets via an "effective local lethal function ", which characterizes the response of each cell line to the spectra of "restricted specific energy".

Study of the Influence of NanOx Parameters.

NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and diffusion of reactive chemical species. In order to further characterize the new framework, we discuss the meaning and relevance of most of the NanOx parameters by evaluating their influence on the linear-quadratic coefficient α and on the dose deposited to achieve 10% or 1% of cell survival, D 10 % or D 1 % , as a function of LET.

Relationship between radioadaptive response and individual radiosensitivity to low doses of gamma radiation: an extended study of chromosome damage in blood lymphocytes of three donors.

Purpose: Our study aimed at evaluating: 1) whether well-established variability in radioadaptive response (AR) in various donor blood lymphocytes might be attributed to inter-individual differences in radiosensitivity to different low dose levels; 2) whether AR is reproducibly present over time in the lymphocytes of AR-positive individuals. Experimental procedure: Whole blood samples of three donors were exposed to low doses (2-30 cGy) of γ-radiation alone (G phase) or followed by a 1 Gy challenge dose (late S/early G phase), and chromosome aberration were scored to assess the dose-response relationship and adaptive response, correspondingly. Three experiments were performed on blood samples of the same donors at six month intervals.

Differential pattern of HIF-1α expression in HNSCC cancer stem cells after carbon ion or photon irradiation: one molecular explanation of the oxygen effect.

Background: Head and neck squamous cell carcinoma (HNSCC) are resistant to standard treatments, partly due to cancer stem cells (CSCs) localised in hypoxic niches. Compared to X-rays, carbon ion irradiation relies on better ballistic properties, higher relative biological effectiveness and the absence of oxygen effect. Hypoxia-inducible factor-1α (HIF-1α) is involved in the resistance to photons, whereas its role in response to carbon ions remains unclear.

Modeling cell response to low doses of photon irradiation: Part 2--application to radiation-induced chromosomal aberrations in human carcinoma cells.

The biological phenomena observed at low doses of ionizing radiation (adaptive response, bystander effects, genomic instability, etc.) are still not well understood. While at high irradiation doses, cellular death may be directly linked to DNA damage, at low doses, other cellular structures may be involved in what are known as non-(DNA)-targeted effects.

Modeling cell response to low doses of photon irradiation--Part 1: on the origin of fluctuations.

Intra- and inter-individual variability is a well-known aspect of biological responses of cells observed at low doses of radiation, whichever the phenomenon considered (adaptive response, bystander effects, genomic instability, etc.). There is growing evidence that low-dose phenomena are related to cell mechanisms other than DNA damage and misrepair, meaning that other cellular structures may play a crucial role.