The Response of Tissues to Very Low Doses per Fraction: A Reflection of Induced Repair?

  • M. C. Joiner
  • B. Marples
  • H. Johns
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 130)


The linear-quadratic (LQ) equation is now used widely to model and predict the increase in total dose with decreasing dose per fraction needed for an isoeffective response to radiotherapy in normal tissues and tumors (Joiner 1989). This relationship reflects the gradual decrease in radiation effectiveness with lowered doses due to these doses being further and further back “on the shoulder” of the underlying survival curve for the cells at risk. Although there has been some indication in experimental studies in vivo that the LQ model can underpredict radiation response to doses per fraction in the range 1–2 Gy relative to higher doses per fraction, this appears to be due to incomplete repair between successive doses (Thames et al. 1988). Alternatively, studies on pig skin have suggested that the LQ model can overpredict radiation effect in the range 2–6 Gy, but this has been attributed to a combination of cellular repopulation and cell cycle redistribution affecting net tissue response (Hopewell and van den Aardweg 1991). Thus for doses greater than 1 Gy per fraction, the LQ model describes the radiation response of normal tissues reasonably well.


Neutron Dose Incomplete Repair Ionize Radiation Damage Cellular Repopulation Radiat Oncol Bioi Phys 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beck-Bornholdt HP, Maurer T, Becker S, Omniczynski M, Vogler H, Wurschmidt F (1989) Radiotherapy of the rhabdomyosarcoma R1H of the rat: hyperfractionation — 126 fractions applied within 6 weeks. Int J Radiat Oncol Biol Phys 16: 701–705PubMedCrossRefGoogle Scholar
  2. Denekamp J (1973) Changes in the rate of repopulation during multifraction irradiation of mouse skin. Br J Radiol 46: 381–387PubMedCrossRefGoogle Scholar
  3. Douglas BG, Fowler JF (1976) The effect of’multiple small doses of X-rays on skin reactions in the mouse and a basic interpretation. Radiat Res 66: 401–426PubMedCrossRefGoogle Scholar
  4. Folkard M (1986) Determination of d(3)-Be and d(4)-Be neutron spectra using a recoil proton spectrometer. Phys Med Biol 31: 135–144CrossRefGoogle Scholar
  5. Hopewell JW, van den Aardweg GJMJ (1991) Studies of dose-fractionation on early and late responses in pig skin: a reappraisal of the importance of the overall treatment time and its effects on radiosensitization and incomplete repair. Int J Radiat Oncol Biol Phys 21: 1441–1450PubMedCrossRefGoogle Scholar
  6. Ikushima T (1987) Chromosomal responses to ionizing radiation reminiscent of an adaptive response in cultured Chinese hamster cells. Mutat Res 180: 215–221PubMedCrossRefGoogle Scholar
  7. Ikushima T (1989) Radio-adaptive response: characterization of a cytogenetic repair induced by low-level ionizing radiation in cultured Chinese hamster cells. Mutat Res 227: 241–246PubMedCrossRefGoogle Scholar
  8. Johns H, Joiner MC (1991) A simple method for fitting curves to dose—effect data for functional damage. Int J Radiat Biol 60: 533–541PubMedCrossRefGoogle Scholar
  9. Joiner MC (1987) The design and interpretation of top-up experiments to investigate the effects of low radiation doses. Int J Radiat Biol 51: 115–130CrossRefGoogle Scholar
  10. Joiner MC (1989) The dependence of radiation response on the dose per fraction. In: McNally NJ (ed) The scientific basis for modern radiotherapy. British Institute of Radiology, London, pp 20–26 (BIR Report 19 )Google Scholar
  11. Joiner MC, Denekamp J (1986) Evidence for a constant repair capacity over 20 fractions of X-rays. Int J Radiat Biol 49: 143–150CrossRefGoogle Scholar
  12. Joiner MC, Johns H (1988) Renal damage in the mouse: the response to very small doses per fraction. Radiat Res 114: 385–398PubMedCrossRefGoogle Scholar
  13. Joiner MC, Denekamp J, Maughan RL (1986) The use of top-up experiments to investigate the effect of very small doses per fraction in mouse skin. Int J Radiat Biol 49: 565–580CrossRefGoogle Scholar
  14. Joiner MC, Rojas A, Johns H (1989) Does the repair capacity of skin change with repeated exposure to X-rays? Int J Radiat Biol 55: 993–1005PubMedCrossRefGoogle Scholar
  15. Joiner MC, Rojas A, Johns H (1992) A test of equal effect per fraction in the kidney of the mouse. Radiat Res 130: 227–235PubMedCrossRefGoogle Scholar
  16. Koval TM (1984) Multiphasic survival response of a radioresistant lepidopteran insect cell line. Radiat Res 98: 642–648PubMedCrossRefGoogle Scholar
  17. Koval TM (1986) Inducible repair of ionizing radiation damage in higher eukaryotic cells. Mutat Res 173: 291–293PubMedCrossRefGoogle Scholar
  18. Koval TM (1988) Enhanced recovery from ionizing radiation damage in a lepidopteran insect cell line. Radiat Res 115: 413–420PubMedCrossRefGoogle Scholar
  19. 19.
    Marples B, Joiner MC (1992) The response of V79 cells to low radiation doses: evidence of enhanced sensitivity of the whole cell population. Radiat Res (in press)Google Scholar
  20. Palcic B, Jaggi B (1986) The use of solid state sensor technology to detect and characterise live mammalian cells growing in tissue culture. Int J Radiat Biol 50: 345–352CrossRefGoogle Scholar
  21. Papathanasiou MA, Kerr NCK, Robbins JH, McBride OW, Alamo I, Barrett SF, Hickson ID, Fornace Ai (1991) Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C. Mol Cell Biol 11: 1009–1016PubMedGoogle Scholar
  22. Parkins CS, Fowler JF (1985) Repair in mouse lung of multifraction X-rays and neutrons: extension to 40 fractions. Br J Radiol 58: 225–241PubMedCrossRefGoogle Scholar
  23. Parkins CS, Fowler JF (1986) The linear quadratic fit for lung function after irradiation with X-rays at smaller doses per fraction than 2 Gy. Br J Cancer 53 [Suppl VII]: 320–323Google Scholar
  24. Parkins CS, Fowler JF, Maughan RL, Roper NU (1985) Repair in mouse lung for up to 20 fractions of X-rays or neutrons. Br J Radiol 58: 225–241PubMedCrossRefGoogle Scholar
  25. Shadley JD, Wiencke JK (1989) Induction of the adaptive response by X-rays is dependent on radiation intensity. Int J Radiat Biol 56: 107–118PubMedCrossRefGoogle Scholar
  26. Shadley JD, Wolff S (1987) Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation. Mutagenesis 2: 95–96PubMedCrossRefGoogle Scholar
  27. Spadinger I, Palcic B (1992) The relative biological effectiveness of 60Co y-rays, 55 kVp X-rays, 250 kVp X-rays and 11 MeV electrons at low doses. Int J Radiat Biol 61: 345–353PubMedCrossRefGoogle Scholar
  28. Stevens G, Joiner MC, Joiner B, Johns H, Denekamp J (1991) Early detection of damage following bilateral renal irradiation in the mouse. Radiother Oncol 20: 124–131PubMedCrossRefGoogle Scholar
  29. Thames HD, Ang KK, Stewart FA, van der Schueren E (1988) Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction? Int J Radiat Biol 54: 13–19PubMedCrossRefGoogle Scholar
  30. Tuschl H, Altmann H, Kovac R, Topaloglou A, Egg D, Gunther R (1980) Effects of low-dose radiation on repair processes in human lymphocytes. Radiat Res 81: 1–9PubMedCrossRefGoogle Scholar
  31. Watts ME, Hodgkiss RJ, Jones NR, Fowler JF (1986) Radiosensitisation of Chinese hamster cells by oxygen and misonidazole at low X-ray doses. Int J Radiat Biol 50: 1009–1021CrossRefGoogle Scholar
  32. Wilson GD, Soranson JA, Lewis AA (1987) Cell kinetics of mouse kidney using bromodeoxyuridine incorporation and flow cytometry: preparation and staining. Cell Tissue Kinet 20: 125–133PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1993

Authors and Affiliations

  • M. C. Joiner
    • 1
  • B. Marples
    • 1
  • H. Johns
    • 1
  1. 1.CRC Gray LaboratoryMount Vernon HospitalNorthwood, MiddlesexUK

Personalised recommendations