Skip to main content
SpringerLink
Log in

The relative biological effectiveness of densely ionizing heavy-ion radiation for inducing ocular cataracts in wild type versus mice heterozygous for the ATM gene

  • Original Paper
  • Published:
Radiation and Environmental Biophysics Aims and scope Submit manuscript

Abstract

The accelerated appearance of ocular cataracts at younger ages has been recorded in both astronauts and airline pilots, and is usually attributed to high-energy heavy ions in galactic cosmic ray radiation. We have previously shown that high-LET 1-GeV/nucleon 56Fe ions are significantly more effective than X-rays in producing cataracts in mice. We have also shown that mice haploinsufficient for ATM develop cataracts earlier than wild-type animals, when exposed to either low-LET X-rays or high-LET 56Fe ions. In this paper we derive quantitative estimates for the relative biological effectiveness (RBE) of high energy 56Fe ions compared with X-rays, both for wild type and for mice haploinsufficient for ATM. There is a clear trend toward higher RBE’s in haploinsufficient animals, both for low- and high-grade cataracts. Haploinsufficiency for ATM results in an enhanced sensitivity to X-rays compared with the wild type, and this enhancement appears even larger after exposure to high-LET heavy ions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Cucinotta FA, Manuel FK, Jones J, Iszard G, Murrey J, Djojonegro B, Wear M (2001) Space radiation and cataracts in astronauts. Radiat Res 156:460–466

    Article  Google Scholar 

  2. Rafnsson V, Olafsdottir E, Hrafnkelsson J, Sasaki H, Arnarsson A, Jonasson F (2005) Cosmic radiation increases the risk of nuclear cataract in airline pilots: a population-based case-control study. Arch Ophthalmol 123:1102–1105

    Article  Google Scholar 

  3. Worgul BV, Merriam GR Jr, Medvedovsky C (1989) Cortical cataract development–an expression of primary damage to the lens epithelium. Lens Eye Toxic Res 6:559–571

    Google Scholar 

  4. Worgul BV (1986) Cataract analysis and the assessment of radiation risk in space. Adv Space Res 6:285–293

    Article  ADS  Google Scholar 

  5. Brenner DJ, Medvedovsky C, Huang Y, Merriam GR Jr, Worgul BV (1991) Accelerated heavy particles and the lens. VI. RBE studies at low doses. Radiat Res 128:73–81

    Article  Google Scholar 

  6. Worgul BV, Medvedovsky C, Huang Y, Marino SA, Randers-Pehrson G, Brenner DJ (1996) Quantitative assessment of the cataractogenic potential of very low doses of neutrons. Radiat Res 145:343–349

    Article  Google Scholar 

  7. Hall EJ, Brenner DJ, Worgul B, Smilenov L (2005) Genetic susceptibility to radiation. Adv Space Res 35:249–253

    Article  ADS  Google Scholar 

  8. Taylor AM, Harnden DG, Arlett CF, Harcourt SA, Lehmann AR, Stevens S, Bridges BA (1975) Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 258:427–429

    Article  ADS  Google Scholar 

  9. Taylor AM, Byrd PJ (2005) Molecular pathology of ataxia telangiectasia. J Clin Pathol 58:1009–1015

    Article  Google Scholar 

  10. Swift M, Morrell D, Cromartie E, Chamberlin AR, Skolnick MH, Bishop DT (1986) The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet 39:573–583

    Google Scholar 

  11. FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA (1997) Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet 15:307–310

    Article  Google Scholar 

  12. Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF (2005) Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97:813–822

    Article  Google Scholar 

  13. Angele S, Hall J (2000) The ATM gene and breast cancer: is it really a risk factor? Mutat Res 462:167–178

    Article  Google Scholar 

  14. Swift M, Morrell D, Massey RB, Chase CL (1991) Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325:1831–1836

    Article  Google Scholar 

  15. Lavin MF, Birrell G, Chen P, Kozlov S, Scott S, Gueven N (2005) ATM signaling and genomic stability in response to DNA damage. Mutat Res 569:123–132

    Google Scholar 

  16. Iliakis G, Wang Y, Guan J, Wang H (2003) DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene 22:5834–5847

    Article  Google Scholar 

  17. Pandita TK, Hittelman WN (1994) Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells. Mutat Res 310:1–13

    Google Scholar 

  18. Hall EJ, Schiff PB, Hanks GE, Brenner DJ, Russo J, Chen J, Sawant SG, Pandita TK (1998) A preliminary report: frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy. Can J Sci Am 4:385–389

    Google Scholar 

  19. Cesaretti JA, Stock RG, Lehrer S, Atencio DA, Bernstein JL, Stone NN, Wallenstein S, Green S, Loeb K, Kollmeier M, Smith M, Rosenstein BS (2005) ATM sequence variants are predictive of adverse radiotherapy response among patients treated for prostate cancer. Int J Radiat Oncol Biol Phys 61:196–202

    Google Scholar 

  20. Worgul BV, Smilenov L, Brenner DJ, Junk A, Zhou W, Hall EJ (2002) Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts. Proc Natl Acad Sci USA 99:9836–9839

    Article  ADS  Google Scholar 

  21. Worgul BV, Smilenov L, Brenner DJ, Vazquez M, Hall EJ (2005) Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes. Adv Space Res 35:254–259

    Article  ADS  Google Scholar 

  22. Zeitlin C, Heilbronn L, Miller J, Rademacher SE, Borak T, Carter TR, Frankel KA, Schimmerling W, Stronach CE (1997) Heavy fragment production cross section from 1.05 GeV/nucleon 56Fe in C, Al, Cu, Pb, and CH2 targets. Phys Rev C Nucl Phys 56:388–397

    ADS  Google Scholar 

  23. Merriam GR Jr, Focht EF (1962) A clinical and experimental study of the effect of single and divided doses of radiation on cataract production. Trans Am Ophthalmol Soc 60:35–52

    Google Scholar 

  24. Brenner DJ, Medvedovsky C, Huang Y, Worgul BV (1993) Accelerated heavy particles and the lens. VIII. Comparisons between the effects of acute low doses of iron ions (190 keV/micron) and argon ions (88 keV/micron). Radiat Res 133:198–203

    Article  Google Scholar 

  25. Kaplan EL, Meier P (1957) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Article  MathSciNet  Google Scholar 

  26. Greenwood M (1926) The natural duration of cancer. Rep Pub Health Med Subj 53:1–26

    Google Scholar 

  27. Akima H (1978) A method of bivariate interpolation and smooth surface fitting for irregularly distributed data points. ACM Trans Math Softw 4:148–159

    Article  MATH  Google Scholar 

  28. Riley EF, Lindgren AL, Andersen AL, Miller RC, Ainsworth EJ (1991) Relative cataractogenic effects of X rays, fission-spectrum neutrons, and 56Fe particles: a comparison with mitotic effects. Radiat Res 125:298–305

    Article  Google Scholar 

  29. Lett JT, Cox AB, Lee AC (1985) Some perspectives on cataractogenesis from heavy charged particles. Radiat Res Suppl 8:S201–S207

    Article  Google Scholar 

Download references

Acknowledgments

This research was supported by NASA Grant No. NAG 9-1519 and by the Office of Science (BER) US Department of Energy Grant No. DE-FG02-03ER63629.

Author information

Authors and Affiliations

  1. Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA

    Eric J. Hall, Lubomir Smilenov, Carl D. Elliston & David J. Brenner

  2. Eye Radiation and Environmental Research Laboratory, Columbia University Medical Center, New York, NY, USA

    Basil V. Worgul

Authors
  1. Eric J. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Basil V. Worgul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lubomir Smilenov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carl D. Elliston
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David J. Brenner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric J. Hall.

Additional information

Dedicated to the memory of Professor Basil V. Worgul, who passed away in January 2006, much missed by all his colleagues.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hall, E.J., Worgul, B.V., Smilenov, L. et al. The relative biological effectiveness of densely ionizing heavy-ion radiation for inducing ocular cataracts in wild type versus mice heterozygous for the ATM gene. Radiat Environ Biophys 45, 99–104 (2006). https://doi.org/10.1007/s00411-006-0052-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00411-006-0052-5

Keywords

Search

Navigation