The influence of fractionation on cell survival and premature differentiation after carbon ion irradiation

Carbon ion radiotherapy/Fractionated irradiation/R-BE/Premature terminal differentiation. To investigate the influence of fractionation on cell survival and radiation induced premature differentiation as markers for early and late effects after X-rays and carbon irradiation. Normal human fibroblasts NHDF, AG1522B and WI-38 were irradiated With 250 kV X-rays, or 266 MeV/u, 195 MeV/u and I I MeV/u carbon ions. Cytotoxicity was measured by a clonogenic survival assay or by determination of the differentiation pattern. Experiments with high-energy carbon ions show that fractionation induced repair effects are similar to photon irradiation. The RBE10 values for clonogenic survival are 1.3 and 1.6 for irradiation in one or two fractions for NHDF cells and around 1.2 for AG1522B cells regardless of the fractionation scheme. The RBE for a doubling of post mitotic fibroblasts (PMF) in the population is I for both single and two fractionated irradiation of NHDF cells. Using I I MeV/u carbon ions, no repair effect can be seen in WI-38 cells. The RBE10 for clonogenic survival is 3.2 for single irradiation and 4.9 for two fractionated irradiations. The RBE for a doubling of PMF is 3.1 and 5.0 for single and two fractionated irradiations, respectively. For both cell lines the effects of high-energy carbon ions representing the irradiation of the skin and the normal tissue in the entrance channel are similar to the effects of X-rays. The fractionation effects are maintained. For the lower energy, which is representative for the irradiation of the tumor region. RBE is enhanced for clonogenic survival as well as for premature terminal differentiation. Fractionation effects are not detectable. Consequently, the therapeutic ratio is significantly enhanced by fractionated irradiation with carbon ions.

Correlation between initial chromatid damage and survival of various cell lines exposed to heavy charged particles

The biophysical characteristics of heavy ions make them a rational source of radiation for use in radiotherapy of malignant tumours. Prior to radiotherapy treatment, a therapeutic regimen must be precisely defined, and during this stage information on individual patient radiosensitivity would be of very great medical value. There are various methods to predict radiosensitivity, but some shortfalls are difficult to avoid. The present study investigated the induction of chromatid breaks in five different cell lines, including one normal liver cell line (L02), exposed to carbon ions accelerated by the heavy ion research facility in Lanzhou (HIRFL), using chemically induced premature chromosome condensation (PCC). Previous studies have reported the number of chromatid breaks to be linearly related to the radiation dose, but the relationship between cell survival and chromatid breaks is not clear. The major result of the present study is that cellular radiosensitivity, as measured by D-0, is linearly correlated with the frequency of chromatid breaks per Gy in these five cell lines. We propose that PCC may be applied to predict radiosensitivity of tumour cells exposed to heavy ions.

Survival and initial chromatid breakage in normal and tumour cells exposed in vitro to gamma rays and carbon ions at the HIRFL

Human hepatoma and normal liver cells were irradiated with C-12(6+) ion beams (linear energy transfer (LET) = 96 keV mu m(-1)) and gamma-rays at the Heavy Ion Research Facility in Lanzhou (HIRFL). The numbers and types of chromatid breaks were detected using the premature chromosome condensation technique. Irradiation with C-12(6+) ions produced a majority of isochromatid break types, while chromatid breaks were dominant for irradiation with gamma-rays. Experimental results showed that the initial level of chromatid breaks is clearly related to the absorbed dose from C-12(6+), ions and gamma-rays. The (12)C(6+)ions are relatively more effective at inducing initial chromatid breaks when compared with the gamma-rays. A relative biological effectiveness (RBE) of about 2.5 resulted for the induction of initial chromatid breaks by C-12(6+) ions relative to gamma-rays in both cell lines.