Might intrinsic radioresistance of human tumour cells be induced by radiation?

Survival measurements were made on six human tumour cell lines in vitro after irradiation with single doses of X rays. Doses up to 5 Gy were used giving surviving fractions down to 20%, but the majority of the measurements were made at doses < 1 Gy. These six cell lines have very different intrinsic radiosensitivities: HT29, Be11, and RT112 are radioresistant with surviving fractions at 2 Gy (SF2) between 60 and 74%, while MeWo, SW48, and HX142 are radiosensitive (SF2 = 3-29%). For all the cell lines, response over the dose range 2-5 Gy showed a good fit to a Linear-Quadratic (LQ) model. However, HT29, Be11, and RT112 cells showed a significant increase in X-ray radiosensitivity at doses below < 1 Gy compared with the prediction extrapolated from a LQ model fitted to the data at higher doses. The LQ model also slightly underpredicted the effect of low-dose X rays in MeWo cells, but the response of SW48 and HX142 cells was well described by the LQ model at all doses, with no evidence of increased low-dose effectiveness. The most plausible explanation for this phenomenon is that it reflects an induced radioresistance so that low doses of X-rays in vitro are more effective per Gy than higher doses, because only at higher doses is there sufficient damage to trigger repair systems or other radioprotective mechanisms. It follows that variation in the amount of inducible radioresistance might explain, in part, differences in intrinsic radiosensitivity above > 1 Gy between cell lines: cells would be intrinsically radiosensitive because they have a diminished inducible response.

[1]  B. Fertil,et al.  In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: cell characterization and correlations with local control and overall survival. , 1994, International journal of radiation oncology, biology, physics.

[2]  P. Deschavanne,et al.  The relationship between potentially lethal damage repair and intrinsic radiosensitivity of human cells. , 1989, International journal of radiation biology.

[3]  B Palcic,et al.  Automated detection and recognition of live cells in tissue culture using image cytometry. , 1989, Cytometry.

[4]  M. Joiner,et al.  Renal damage in the mouse: the response to very small doses per fraction. , 1988, Radiation research.

[5]  M. Lindstrom,et al.  Loss of local control with prolongation in radiotherapy. , 1992, International journal of radiation oncology, biology, physics.

[6]  R. Mitchel,et al.  Inducible DNA-repair systems in yeast: competition for lesions. , 1987, Mutation research.

[7]  B. Marples,et al.  The elimination of low-dose hypersensitivity in Chinese hamster V79-379A cells by pretreatment with X rays or hydrogen peroxide. , 1995, Radiation research.

[8]  B. Fertil,et al.  Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves. , 1985, International journal of radiation oncology, biology, physics.

[9]  B. Wouters,et al.  The response of a human tumor cell line to low radiation doses: evidence of enhanced sensitivity. , 1994, Radiation research.

[10]  B. Fertil,et al.  Predictive value of in vitro radiosensitivity parameters in head and neck cancers and cervical carcinomas: preliminary correlations with local control and overall survival. , 1993, International journal of radiation oncology, biology, physics.

[11]  J. Arrand,et al.  Hypersensitive response of normal human lung epithelial cells at low radiation doses. , 1994, International journal of radiation biology.

[12]  P. Lambin,et al.  The effect of the hypoxic cell drug SR-4233 alone or combined with the ionizing radiations on two human tumor cell lines having different radiosensitivity. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[13]  G. Steel,et al.  The radioresponsiveness of human tumours and the initial slope of the cell survival curve. , 1984, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  A. Giaccia,et al.  The use of asymmetric-field inversion gel electrophoresis to predict tumor cell radiosensitivity. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  A. Rainbow,et al.  γ-Ray enhanced reactivation of γ-irradiated adenovirus in human cells , 1979 .

[16]  B. Fertil,et al.  Inherent cellular radiosensitivity as a basic concept for human tumor radiotherapy. , 1981, International journal of radiation oncology, biology, physics.

[17]  S. A. Roberts,et al.  Intrinsic radiosensitivity and prediction of patient response to radiotherapy for carcinoma of the cervix. , 1993, British Journal of Cancer.

[18]  P. Lambin,et al.  Multiphasic survival curves for cells of human tumor cell lines: induced repair or hypersensitive subpopulation? , 1994, Radiation research.

[19]  M. Hannan,et al.  Observations and an interpretation of dose-response relationships for cellular transformation in terms of induced (T) repair. , 1991, International journal of radiation biology.

[20]  B Palcic,et al.  Cell survival measurements at low doses using an automated image cytometry device. , 1993, International journal of radiation biology.

[21]  C. M. Pujara,et al.  Study of the inflexion of x-radiation survival curves for synchronized cell populations of the green alga (Oedogonium cardiacum). , 1969, Radiation research.

[22]  T. M. Koval Inducible repair of ionizing radiation damage in higher eukaryotic cells. , 1986, Mutation research.

[23]  B. Marples,et al.  The response of Chinese hamster V79 cells to low radiation doses: evidence of enhanced sensitivity of the whole cell population. , 1993, Radiation research.

[24]  H D Thames,et al.  Does variation in the in vitro cellular radiosensitivity explain the shallow clinical dose-control curve for malignant melanoma? , 1990, International journal of radiation biology.

[25]  P. Lambin,et al.  Hypersensitivity of a human tumour cell line to very low radiation doses. , 1993, International journal of radiation biology.

[26]  P. Hanawalt,et al.  Carcinogens enhance survival of UV-irradiated simian virus 40 in treated monkey kidney cells: induction of a recovery pathway? , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[27]  B Palcic,et al.  The use of solid-state image sensor technology to detect and characterize live mammalian cells growing in tissue culture. , 1986, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[28]  T. McMillan,et al.  The Intrinsic α/β Ratio for Human Tumour Cells: Is It a Constant? , 1992 .

[29]  JJ Eady,et al.  Host cell reactivation of gamma-irradiated adenovirus 5 in human cell lines of varying radiosensitivity. , 1992, British Journal of Cancer.

[30]  B. Marples,et al.  A preliminary investigation into the extent of increased radioresistance or hyper-radiosensitivity in cells of hamster cell lines known to be deficient in DNA repair. , 1994, Radiation research.

[31]  S. B. Bhattacharjee,et al.  Induction of repair functions by hydrogen peroxide in Chinese hamster cells. , 1988, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[32]  M. Joiner Induced radioresistance: an overview and historical perspective. , 1994, International journal of radiation biology.

[33]  I. Radford The level of induced DNA double-strand breakage correlates with cell killing after X-irradiation. , 1985, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[34]  D. Boreham,et al.  DNA lesions that signal the induction of radioresistance and DNA repair in yeast. , 1991, Radiation research.

[35]  G. Sanguineti,et al.  In vivo cell kinetics in head and neck squamous cell carcinomas predicts local control and helps guide radiotherapy regimen. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  A. Rainbow,et al.  U.V. enhanced reactivation of U.V.-and gamma-irradiated adenovirus in normal human fibroblasts. , 1983, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[37]  S. Davidson,et al.  Prediction of cervical carcinoma response to radiotherapy , 1991, The Lancet.

[38]  C. West,et al.  Invited review: intrinsic radiosensitivity as a predictor of patient response to radiotherapy. , 1995, The British journal of radiology.

[39]  H. Thames,et al.  Clinical evidence for tumor clonogen regeneration: interpretations of the data. , 1991, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[40]  N. Chavaudra,et al.  The initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine. , 1989, International journal of radiation oncology, biology, physics.

[41]  S. Powell,et al.  The repair fidelity of restriction enzyme-induced double strand breaks in plasmid DNA correlates with radioresistance in human tumor cell lines. , 1994, International journal of radiation oncology, biology, physics.

[42]  B. Marples,et al.  The response of Chinese hamster V79-379A cells exposed to negative pi-mesons: evidence that increased radioresistance is dependent on linear energy transfer. , 1994, Radiation research.

[43]  S. Wolff,et al.  Failla Memorial Lecture. Is radiation all bad? The search for adaptation. , 1992, Radiation research.

[44]  R. Mortimer,et al.  The relation of radioresistance to budding in Saccharomyces cerevisiae. , 1954, Archives of biochemistry and biophysics.

[45]  W A Brock,et al.  Initial slope of radiation survival curves is characteristic of the origin of primary and established cultures of human tumor cells and fibroblasts. , 1987, Radiation research.

[46]  T. M. Koval Multiphasic survival response of a radioresistant lepidopteran insect cell line. , 1984, Radiation research.

[47]  P. Lambin,et al.  Mégafractionnement: une méthode pour agir sur les tumeurs intrinsèquement radiorésistantes? , 1993 .

[48]  P. Lambin,et al.  The effect of very low radiation doses on the human bladder carcinoma cell line RT112. , 1994, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.