| Douglas R. Boreham |
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Professor
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ResearchResearch Interests Areas of Research
Most Significant Contributions to Research (1) DISCOVERED that developing mouse fetuses could be protected against the teratogenic effects of in utero irradiation by prior exposure to low doses of radiation or mild heat. This response was dependent on functional p53 activity. The research examined hundreds of pregnant females and over five thousand fetuses. The work demonstrated that radiation risk is not fixed and can be modified by external stimuli. It also showed that genetic factors play an important role in radiation risk. Radiation protection regulations have special standards relating to pregnant nuclear energy workers and fetuses. This research will support a better understanding of low dose radiation effects on the unborn child and should help in developing future protection policy for pregnant workers (see Research Contribution Section ref.1,2,3). (2) REVEALED for the first time that there was a bystander effect for low LET gamma-radiation. Bystander effects have been a major focus of current radiation biology research because it seems that cells that have not been directly hit by radiation can still be affected by radiation when they are in the vicinity of irradiated cells. This work has tremendous importance with respect to radiation health risk assessment because it indicates that the actual target size for radiation effects may be much larger than previously suspected. However, previous work on bystander effects used high LET alpha particle microbeams to show that negative effects could be measured in unirradiated cells. Our research showed that a bystander effect existed for low LET irradiations but that the influence on nearby cells was a positive protective effect (ref 10). Therefore radiation risk may not be increased by the bystander effect for low LET radiation but may decrease risk, which is important to understand for human health risk assessment if sound radiation protection policies are to be instituted. (3) CREATED a modified assay to quantify radiation damage and cell death by apoptosis in human lymphocytes. This research was the first to report that apoptosis in human lymphocytes could be used for biological dosimetry. Later this work showed that apoptosis could predict individual radiation sensitivity and we are currently applying our expertise in the cancer clinic to utilize apoptosis as a predictive assay to identify individuals at risk for adverse reactions to radiation therapy. Additional research demonstrated for the first time that apoptosis also showed a dose rate effect at very low dose rates (previously published results showed no dose rate effect for induction of apoptosis however the dose rates used were higher than in our experiments). Therefore, this research impacts radiation health risk estimation because apoptosis is an important protective mechanism against detrimental radiation effects (ref. 5,9,14,17). (4) OPTIMIZED a molecular cytogenetic technique using confocal microscropy to show that homologous chromosome domains within a human cell nucleus rearrange their spatial distribution to be in close proximity after exposure to radiation (ref 15). This was an early result that supported the contention that homologous recombinational repair (HRR) may occur in human cells after radiation. Prior to this work, there was little evidence that HHR occurred in mammalian cells. Our work using yeast showed that HHR played a major role for cells to adapt and become resistant to radiation (Boreham et al. 1990, Radiat. Res 123:203-212, Boreham et al. 1991, Radiat Res. 128:19-28, Boreham et al. 1994, Radiat. Res. 137:190-195, ref. 8,12). Recent research by others has now demonstrated the importance of HHR in mammalian responses to radiation and supports our original observations that HHR has an important role in protecting human cells from radiation. (5) DEMONSTRATED for the first time that latency period for radiation-induced cancer in mice could be extended by mild heat or low dose radiation exposure. This research was an innovative and practical extension of adaptive response research from basic radiation biology research. This work showed that the risk of death caused by cancer is not constant and can be modified by biological processes influenced by the adaptive response (ref 11, 20). PublicationsPublications 1. Thompson JW, Burdette KE, Inrig EL, Dewitt R, Mistry R, Rink WJ, Boreham DR. "Optically stimulated luminescence dosimetry with gypsum wallboard (Drywall)". Radiat. Prot. Dosimetry. 2010 May 6. [Free pdf,doi] 2. Zhang Z, Zhu W, Lapolla SM, Miao Y, Shao Y, Falcone M, Boreham D, McFarlane N, Ding J, Johnson AE, Zhang XC, Andrews DW, Lin J. Zhang Z, Zhu W, Lapolla SM, Miao Y, Shao Y, Falcone M, Boreham D, McFarlane N, Ding J, Johnson AE, Zhang XC, Andrews DW, Lin J. "Bax forms an oligomer via separate, yet interdependent surfaces" J Biol Chem. 2010 Apr 9. [Free pdf, doi] 3. Schnarr K, Boreham D, Sathya J, Julian J, Dayes IS. "Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients". Int J Radiat Oncol Biol Phys. 2009 Aug 1; 74(5):1424-30. [doi] 4. Werbowetski-Ogilvie TE, Bossé M, Stewart M, Schnerch A, Ramos-Mejia V, Rouleau A, Wynder T, Smith MJ, Dingwall S, Carter T, Williams C, Harris C, Dolling J, Wynder C, Boreham D, Bhatia M. "Characterization of human embryonic stem cells with features of neoplastic progresion". Nat Biotechnol.2009 Jan; 27(1):91-7. [doi] 5. Lemon JA, Rollo CD, McFarlane NM, Boreham DR. "Radiation-induced apoptosis in mouse lymphocytes is modified by a complex dietary supplement: the effect of genotype and gender". Mutagenesis. 2008 Nov; 23(6):465-72. [Free pdf, doi] 6. Lemon JA, Rollo CD, Boreham DR. "Elevated DNA damage in a mouse model of oxidative stress: impacts of ionizing radiation and a protective dietary supplement". Mutagenesis. 2008 Nov; 23(6):473-82. [Free pdf, doi] 7. Boreham DR, Dolling JA. "Risks associated with therapeutic 131I radiation exposure". J Nucl Med. 2008 May; 49(5):691-3. [Free pdf, doi] 8. Kilemade M, Lemon J, Boreham D. "Characteristics of the adaptive response in cultured salmon cells exposed to ionizing radiation". Environ Mol Mutagen. 2008 Apr; 49(3):165-72. [doi] 9. Schaffer P, Gleave JA, Lemon JA, Reid LC, Pacey LK, Farncombe TH, Boreham DR, Zubieta J, Babich JW, Doering LC, Valliant JF. "Isostructural fluorescent and radioactive probes for monitoring neural stem and progenitor cell transplants". Nucl Med Biol. 2008 Feb; 35(2):159-69. [doi] 10. Scott BR, Sanders CL, Mitchel REJ, Boreham DR. "CT scans may reduce rather than increase risk of cancer". Journal of American Physicians and Surgeons, Vol. 13, Number 1, 2008 (accepted 07). [link] 11. Casidy, C., Lemon, J.A., Boreham, D.R. "Impacts of low-dose gamma-radiation on genotoxic risk in aquatic ecosystems". Dose-Response 2007 Nov 23; 5(4):323-32. [Free pdf, doi] 12. Schnarr K, Dayes I, Sathya J, Boreham D. "Individual radiosensitivity and its relevance to health physics". Dose Response. 2007 Nov 23; 5(4):333-48. [Free pdf, doi] 13. Higson DJ, Boreham DR, Brooks AL, Luan YC, Mitchel RE, Strzelczyk J, Sykes PJ. "Effects of low doses of radiation: joint statement from the following participants at the 15 pacific basin nuclear conference, sessions held in Sydney, Australia, Wednesday 18 October 2006". Dose Response. 2007 Sep 30; 5(4):259-62. [Free pdf, doi] 14. Wilkinson, D., Segura, T., L. Prud’homme-Lalonde, Mullins, D., Lachapelle, S., Qutob, S., Thorleifson, E., Wilkins, R., Dolling, J-A, Boreham, D. "Canadian capacity for response to radiation emergencies".Radiation Measurements 2007; Vol 22, pp 23-29. [doi] 15. Miller, S.M., Ferrarotto, C.L., Vlahovich, S., Wilkins, R.C., Boreham, D.R. and Dolling, J-A. "Canadian Cytogenetic Emergency Network (CEN) for biological dosimetry following radiological/nuclear accidents".Int. J. Radiat. Biol. 2007; Vol 72, pp 187-193. [doi] 16. Dolling, J-A and D.R. Boreham. "Radiological emergency response: The national biological dosimetry response plan". Dose Response. 2007; 5:76-79. [Free pdf, doi] 17. Covey SD, Brunet RH, Gandhi SG, McFarlane N, Boreham DR, Gerber GE, Trigatti BL. "Cholesterol depletion inhibits fatty acid uptake without affecting CD36 or caveolin-1 distribution in adipocytes".Biochem Biophys Res Commun. 2007 Feb 2; [Epub ahead of print], PMID: 17291449 [PubMed – as supplied by publisher]. [doi] 18. Zhang Y, Ahmed AM, McFarlane N, Capone C, Boreham DR, Truant R, Igdoura SA, Trigatti BL. "Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways". J Lipid Res 2007; 48(2):405-16. [Free pdf, doi] 19. Zhang Y, Ahmed AM, Tran TL, Lin J, McFarlane N, Boreham DR, Igdoura SA, Truant R, Trigatti BL. "The inhibition of endocytosis affects HDL-lipid uptake mediated by the human scavenger receptor class B type I". Mol. Membr. Biol. 2007 Sep-Dec; 24(5-6):442-54. [doi] 20. Boreham DR, Dolling JA, Somers C, Quinn J, Mitchel RE. "The adaptive response and protection against heritable mutations and fetal malformation". Dose Response. 2006 Aug 25; 4(4):317-26. [Free pdf, doi] 21. Zarate N, Wang XY, Whaite EJ, Boreham D, Rangachari PK, Huizinga JD. "Low doses of ionizing radiation can prevent radiation-induced colonic epithelia hyporesponsiveness to muscarinic agonists." Int J Radiat Biol. 2006; 82(12):887-98. [doi] 22. Dixit D, Zarate N, Liu LW, Boreham DR, Huizinga JD. "Interstitial cells of Cajal and adaptive relaxation in the mouse stomach". Am J Physiol Gastrointest Liver Physiol. 2006; 291(6):G1129-36. [Free pdf, doi] 23. Ryan LA, Wilkins RC, McFarlane NM, Sung MM, McNamee JP, Boreham DR. "Relative biological effectiveness of 280 keV neutrons for apoptosis in human lymphocytes". Health Phys. 2006; 91(1):68-75. [doi] 24. Liberda JJ, Schnarr K, Coulibaly P, Boreham DR. "Artificial neural network modeling of apoptosis in gamma irradiated human lymphocytes". Int. J Radiat. Biol. 2005; 81(11):827-40. [doi] 25. K.A. Stephenson, J. Zubieta, S.R. Banerjee, M.K. Levadala, L. Taggart, L. Ryan, N. McFarlane, D.R. Boreham, J. Babich, and J.F. Valliant. "A new strategy for the preparation of peptid-Targeted Radiopharmaceuticals based on an Fmoc-Lysine-Derived Single Amino Acid Chelate (SAAC). Automated solid-phase synthesis, NMR characterization and In vivo Screening of fMLF(SAAC)G and fMLF[(SAAC-Re(CO)3)+]". Bioconjug Chem. 2005; 15:128-36. [doi] 26. Stephenson KA, Banerjee SR, Sogbein OO, Levadala MK, McFarlane N, Boreham DR, Maresca KP, Babich JW, Zubieta J, Valliant JF. "A new strategy for the preparation of peptide-targeted technetium and rhenium radiopharmaceuticals. The automated solid-phase synthesis characterization, labelling and screening of a peptide-ligand library targeted at the formyl peptide receptor". Bioconjug. Chem. 2005 Sep-Oct; 16(5):1189-95. [doi] 27. Lemon, J.A., Boreham, D.R., Rollo, C.D. "A complex dietary supplement extends longevity of mice". J. Gerontol A. Biol. Sci. Med. Sci. 2005; 60(3):275-9. [Free pdf, doi] 28. Rao F.H. Khan, J, Pekar, W.J. Rink, and D.R. Boreham. "Retrospective radiation dosimetry using electron paramagnetic resonance in canine dental enamel". Appl. Radiat. Isot. 2005; 62, 173-179. [doi] 29. Somers, CM., Sharma, R., Quinn, JS., Boreham, D.R. "Gamma radiation-induced heritable mutations at repetitive DNA loci in out bred mice". Mutat Res. 2004; 568(1):69-78. [doi] 30. K.A. Stephenson, S.R. Banerjee, T. Besanger, O.O. Sogbein, M. K. Levadala, N. McFarlane, J.A. Lemon,D.R. Boreham, K.P. Maresca, J.D. Brennan, J. Babich, J. Zubieta and J.F. Valliant. "Bridging the gap between in vitro and in vivo imaging: isostructural Re and 99mTc complexes for correlating fluorescence and radioimaging studies". J Am Chem Soc. 2004; 126:8598-8599. [doi] 31. B. A. Ulsh, S. M. Miller, F. F. Mallory, R. E. J. Mitchel, D. P. Morrison, and D. R. Boreham. "Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation". Journal of Radioactivity. 2004; 74:73-81. [doi] 32. Lemon, J.A. and D.R. Boreham. "McIARS/COG Workshop on networking radiation sciences in health safety and the environment". International Journal of Radiation Biology. 2004; 80:83-89. [doi] 33. Rao F.H. Khan, Aslam, W.J. Rink, and D.R. Boreham. “Electron paramagnetic resonance dose response studies for neutron irradiated human tooth enamel”. Nucl. Instrum. Meth. B. 62. 2004; 528-534. [doi] 34. R.F.H. Khan, W.J. Rink, and D.R. Boreham. "Biophysical dose measurement using electron paramagnetic resonances in rodent teeth". Appl. Radiat. Isot. 59. 2003; 189-196. [doi] 35. J.A. Lemon, D.R. Boreham, and C.D. Rollo. "A dietary supplement abolishes age related cognitive decline in transgenic mice with elevated free radical processes". Experimental Biology and Medicine. 2003; 228(7) 800-810. [Free pdf] 36. R.F.H. Khan, D.R. Boreham and W.J. Rink. "Quantification of low amplitude dosimetric signal in EPR teeth dosimetry – a novel approach". Rad. Prot. Dosim. 2003; 103(4) 359-362. [pdf] 37. K.J. Wilson, D. Boreham, G.R. Moran. "Applications of radiation within the wine industry”. Canadian Undergraduate Physics Journal, January 2003. [pdf] 38. D.R. Boreham, J-A- Dolling, J. Misonoh, R.E.J. Mitchel. "Radiation-induced teratogenic effects in fetal mice with varying Trp53 function: Influence of prior heat stress". Radiation Research. 2002; 158(4):449-457. [doi] 39. D.R. Boreham, J-A Dolling, J. Misonoh, and R.E.J. Mitchel. "Teratogenic effects of mild heat stress during mouse embryogenesis: Effect of Trp53". Radiation Research. 2002; 158(4):443-8. [doi] 40. R.E.J Mitchel, J-A Dolling, J. Misonoh, J-A, M.E. Bahen and D.R. Boreham. "Influence of prior exposure to low dose adapting radiation on radiation-induced teratogenic effects in fetal mice with varying Trp53 function". Radiation Research. 2002; 158(4):458-63. [doi] 41. D.R. Chettle, D.R. Boreham, F.E. McNeill, and W.V. Prestwich. "Medical Physics Education at the Undergraduate Level". Physica Medica. 2001; Vol. XVII, 66-68. 42. J-A. Dolling, D.R. Boreham, M.E. Bahen, R.E.J. Mitchel. "Role of Rad9-dependent cell cycle checkpoints in the adaptive response to ionizing radiation in yeast, Saccharomyces cerevisiae".International Journal of Radiation Biology. 2000; 76, 1273-1279. [doi] 43. D.R. Boreham, J-A Dolling, S.R. Maves, N. Siwarungson, and R.E.J. Mitchel. "Dose rate effects for apoptosis and micronucleus formation in gamma-irradiated human lymphocytes". Radiation Research.2000; 153:579-586. [doi] 44. D.R. Boreham, J-A Dolling, J. Broome, S.R. Maves, B.P. Smith and R.E,J. Mitchel. "Cellular adaptive response to single tracks of low-LET radiation and the effect on non-irradiated neighboring cells".Radiation Research. 2000; 153, 230. 45. R.E.J. Mitchel, J.S. Jackson, R.A. McCann, D.R. Boreham. "The adaptive response modifies latency period for radiation-induced myeloid leukemia in CBA/H Mice". Radiation Research. 1999, 152, 273-279. 46. J-A Dolling, D.R. Boreham, D.L. Brown, G.P. Raaphorst and R.E.J. Mitchel. "Cisplatin-modification of DNA repair and ionizing radiation lethality in yeast". Saccharomyces cerevisiae, Mutation Research. 1999; 433, 127-136. [doi] 47. J-A Dolling, D.R. Boreham, D.L. Brown, R.E.J. Mitchel, G.P. Raaphorst. "Modulation of radiation-induced strand break repair by Cisplatin in mammalian cells". Int. J. Radiat. Res. 1998, 74 (1) 61-69. [doi] 48. D.R. Boreham, J-A. Dolling, S.R. Maves, S. Miller, D.P. Morrison, R.E.J. Mitchel. "Heat-induced thermal tolerance and radiation resistance to apoptosis in human lymphocytes". Biochem. Cell Biol. 1997; 75, 7-11. [doi] 49. J-A Dolling, D.R. Boreham, D.L. Brown, G.P. Raaphorst, and R.E.J. Mitchel. "Rearrangement of human cell homologous chromosome domains in response to ionizing radiation". Int. J. Radiat. Biol. 1997; 72(3): 303-311. [doi] 50. J-A. Walker, D.R. Boreham, P. Unrau and A.M.V. Duncan. "Chromosome content and ultrastructure of radiation-induced micronuclei". Mutagenesis. 1996; 11(5): 419-424. [Free pdf] 51. D.R. Boreham, K. Gale, S. Maves, J.A. Walker and D.P. Morrison. "Radiation-induced apoptosis in human lymphocytes: Potential as a biological dosimeter". Health Physics. 1996; 71(5), 685- 691. 52. J.D. Knox, D.R. Boreham, J-A. Walker, D.P. Morrison, L.M. Matrisian, R.B. Nagle, and T. Bowden. "Mapping of the metalloproteinase gene matrilysin to the human chromosome 11q22-23". Cytogenetics and Cell Genetics. 1996; 72, 179-182. 53. D.R. Boreham, H.C. Gasmann and R.E.J. Mitchel. "Waterbath hyperthermia is a simple home use therapy for Psoriasis and also stimulates skin tanning in response to sunlight". International Journal of Hyperthermia. 1995; 11, 745-754. [doi] 54. D.R. Boreham and R.E.J. Mitchel. "Regulation of heat and radiation stress responses in yeast by Hsp-104". Radiation Research. 1994;137, 190-195. [link] 55. S.R. Cregan, D.R. Boreham, P.R. Walker, D.L. Brown and R.E.J. Mitchel. "Modification of radiation-induced apoptosis in radiation or hyperthermia adapted human lymphocytes". Biochem. Cell Biol. 1994; 72, 475-482. 56. D.R. Boreham and R.E.J. Mitchel. "DNA repair in Chlamydomonas reinhardtti induced by heat shock and gamma radiation". Radiation Research. 1993; 135, 365-371. [link] 57. D.R. Boreham and R.E.J. Mitchel. "DNA lesions that signal the induction of radioresistance and DNA repair in yeast". Radiation Research. 1991; 128, 19-28. [link] 58. D.R. Boreham, A. Trivedi, P. Weinberger and R.E.J. Mitchel, 1990. "The involvement of Topoisomerases and DNA Polymerase I in the mechanism of induced thermal and radiation resistance in yeast". Radiation Research. 1990; 123, 203-212. [link] MultimediaNewspapers Scientists find low-dose radiation a benefit - The Hamilton Spectator [link] Nuclear power safe, says expert - The Advertiser [link] Experts call for more study into body scanners - The Globe And Mail [link] Bruce Power open house gets tongues wagging - Daily Herald [link] Radiation Roulette - CBC Canada [link] Bruce scientist argues some radiation is good - The Record-Gazette [link] Public's fear of radiation big hurdle: professor - Simcoe Reformer [link] Movies - Videos Spotlight with Dr. Evil/Batman - Microbeam [link] CT Scans and Exercise - Can They Reduce Cancer Risk? 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