Abstract

Mammalian cells cultured in vitro will be used for studies of low dose rate irradiaton.
Some aims have pragmatic usefulness in radiotherapy but the principal thrust is a more basic understanding of the interaction of radiation with biological material. The present study of the Relative Biological Effectiveness (RBE) of Iodine-125 will be extended to include mitotic delay as an endpoint, because of the observation that RBE values are higher for tumor cells which maintain a high growth fraction in plateau phase. The radiobiological properties of Americium-241 at low dose rate will be studied because of its potential use in brachytherapy. Its low energy emission reduces problems of protection, while its 400 year half-life makes it more economic than Iodine-125 for temporary implants. A variety of cells of human origin will be used both normal and malignant, to assess the relative role of potentially lethal and sublethal damage repair in the response to low dose-rate. Our limited studies to date indicate that PLDR is more important and SLDR less important in human than in rodent cells, and also that PLDR occurs in normal as well as malignant cells. Low dose rate irradiation will be used to predict the initial slope of the acute survival curve and where possible correlated with clinical responsiveness in a range of human tumor cell lines. Genetically deficient human cells will be studied, specifically cells from patients suffering from Ataxia Telangectasia, Xeroderma Pigmentosum, Bloom's Syndrome and 5-oxoprolinurea. The role of halogenated pyrimidines as sensitizers with low dose rate irradiation as used in brachytherapy will be studied. The possibility that incorporated IUdR or BUdR may interact strongly with the soft emission from Iodine-125 or Americium-241 will be investigated. The preliminary observation that the mix of different types of chromosome aberrations varies with dose will be investigated. In particular an attempt will be made to assess whether the spectrum of chromosome aberrations is the same for high doses at low dose rate as for low doses in acute exposures. This investigation bears on the validity of the hypothesis that the low dose rate survival curve is an extrapolation of the initial slope of the acute survival curve.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA024232-12
Application #
3166380
Study Section
Radiation Study Section (RAD)
Project Start
1978-09-01
Project End
1991-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

Brenner, David J; Martinez, Alvaro A; Edmundson, Gregory K et al. (2002) Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue. Int J Radiat Oncol Biol Phys 52:6-13
Brenner, D J; Little, J B; Sachs, R K (2001) The bystander effect in radiation oncogenesis: II. A quantitative model. Radiat Res 155:402-8
Ponomarev, A L; Cucinotta, F A; Sachs, R K et al. (2001) Monte Carlo predictions of DNA fragment-size distributions for large sizes after HZE particle irradiation. Phys Med 17 Suppl 1:153-6
Brenner, D J; Miller, R C (2001) Long-term efficacy of intracoronary irradiation in inhibiting in-stent restenosis. Circulation 103:1330-2
Ponomarev, A L; Cucinotta, F A; Sachs, R K et al. (2001) Extrapolation of the dna fragment-size distribution after high-dose irradiation to predict effects at low doses. Radiat Res 156:594-7
Brenner, D J; Sachs, R K (2000) Protraction effects in radiation studies: basic biophysics. Radiat Res 154:736-7
Brenner, D J; Hall, E J (1999) Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys 43:1095-101
Rakovitch, E; Mellado, W; Hall, E J et al. (1999) Penclomedine-induced DNA fragmentation and p53 accumulation correlate with reproductive cell death in colorectal carcinoma cells with altered p53 status. Oncol Rep 6:161-5
Brenner, D J; Leu, C S; Beatty, J F et al. (1999) Clinical relative biological effectiveness of low-energy x-rays emitted by miniature x-ray devices. Phys Med Biol 44:323-33
Brenner, D J (1999) Does fractionation decrease the risk of breast cancer induced by low-LET radiation? Radiat Res 151:225-9

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