Mark Hill Ph.D., MSc, BSc, CPhys, CRadP, MinistP, MSR, MIPEM
Everybody is exposed to ionising radiation throughout his or her life, either from natural sources, most notably radon gas, or artificial sources, such as medical exposures. Ionising radiation can cause malignant diseases in people exposed to it and inherited defects in later generations. However, exposure to radiation can also be beneficial and is widely used in medicine for both diagnosis (diagnostic radiology and nuclear medicine) and in the treatment of cancer (radiotherapy). Increased understanding of the mechanisms of radiation damage and response is important, not only to improve the assessment of the risk associated with exposure but also in optimising cancer treatment. Additionally the benefit of any medical examination using ionizing radiation has to be weighed up against the inherent risk associated with an exposure.
Exposure to ionising radiation produces a great diversity of chemical, biochemical, cellular, tissue and whole body responses. The subsequent response not only depends on the amount of energy deposited by radiation but on the pattern of energy deposition along individual radiation tracks along with the temporal and spatial distribution of these tracks. The main emphasis of the research is to assess and formulate mechanisms linking the temporal and spatial pattern of energy deposition events on the scale of DNA, cells and tissues to subsequent biological response (including DNA damage and repair, chromosome, aberration formation, cell death, transformation, genomic instability and cellular signalling). This is then interpreted in the context of risk associated with low level exposures or radiotherapy where new treatment procedures such as the use of proton or ion therapy or radio-labelled ligands rely on the track structure properties of these radiations to lead to therapeutic gain (killing the cancer cells while minimising damage in normal tissues).
Schematic of alpha-particle track interacting with DNA, producing clustered damage
Localization of repair proteins (RAD51) to damage in a cell nucleus following alpha-particle traversal
Radiation Sources and Facilities
The Radiation Biophysics Core also facilitates radiation work across the Institute by providing a range of radiation resources and expertise. Department irradiation facilities include gamma-ray irradiators, diagnostic and orthovoltage x-rays, a range of monoenergetic ultrasoft x-rays, pulsed linac (B Vojovic's Group), alpha-particle irradiator and a SARRP image-guided pre-clinical x-ray irradiator.
X-ray sets: A 225kV & 320kV cabinet x-ray irradiators are located in the RRI and housed within shielded room with the ORCRB is 50kV x-ray set and a gantry mounted 260kV x-ray set. These x-ray sets may also be used to partially irradiate samples.
Gamma irradiators: 137Cs irradiators are located in both the RRI and ORCRB
Ultrasoft X-ray sources: Capable of producing a range of characteristic ultrasoft X-rays: CK (0.28keV), AlK (1.49keV), CuL (0.96keV) & TiK (4.55keV) with dose rates up to ~50 Gy min-1. The low energy electrons track-ends produced are similar to those produced by all low-LET radiation and are believed to dominate the biological effect. Techniques have been developed to partially irradiate samples not only over millimetre distances but also micron distance (i.e. sub-nuclear dimensions).
Alpha-particle irradiator: This provides an excellent tool for studying the biological effects of high-LET radiation. Dose rates from 20 Gy min-1 down to <10-4 Gy min-1 are available with the incident energy (and LET) variable from 4.2 MeV down to the Bragg Peak and below.
SARRP Image guided pre-clinical irradiator: Samples may be imaged using cone beam CT prior to targeting and irradiating with sub-millimetre accuracy from a number of angles after treatment planning. The Advanced Technology Group (lead by B. Vojnovic) are developing techniques to extend the capabilities of this irradiator.
Linear accelerator: A pulsed 6MeV linac has been developed by B. Vojnovic’s Group for radiation chemistry/biology studies with sub-microsecond electron pulses and high dose rates.
- Luke Bird, Research Assistant
- Francesca Fiorini, Research Assistant
- Dr James Thompson, Radiation Facilities & Lab Manager
Mark Hill is the Radiation Biophysics Core Leader in the CRUK/MRC Oxford Institute for Radiation Oncology within the Department of Oncology at the University of Oxford. His main research interests are investigating how and why ionising radiation initiates a diverse range of biological responses and the significance of differences in radiation track structure associated with different qualities of ionising radiation. Increased understanding of the mechanisms underpinning the radiation action on biological systems is important in understanding, not only risks associated with low dose exposure, but also in optimising radiotherapy treatment of cancer.
Mark has a BSc Honours degree in Physics from Nottingham University and an MSc and PhD in Radiation Physics at St. Bartholomew’s Medical College and Queen Mary & Westfield College respectively, both part of the University of London. After 3 years postdoctoral research in London he moved to the Medical Research Council’s Radiation & Genome Stability Unit (formally the Radiobiology Unit) at Harwell in Oxfordshire in 1994 and become Head of the Biophysics Group in 2001. In 2008 the Unit joined forces with the Gray Cancer Institute and the University of Oxford to become part of the Radiation Oncology & Biology Initiative at the University of Oxford, relocated to a new building next to the Churchill Hospital in Oxford.
Mark has been involved with a number of committees including being a member of the several IARC working groups preparing the monograph on ionising radiation and cancer, a member of the ICRU working group on the dosimetry of low-dose exposures of ionsing radiation, a member of the tritium sub-group of the UK Advisory Group on Ionizing Radiation (AGIR) and is secretary of the Association for Radiation Research. Mark is also currently the chief examiner for the MSc course in Radiation Biology at the University of Oxford.
- 2008 Head of Radiation Biophysics, Gray Institute for Radiation Oncology & Biology, University of Oxford
- 2001 - 2008 Head of Biophysics Group, MRC Radiation & Genome Stability Unit,
- 2002 Visiting Fellow at Reading University
- 1995 - 2001 Non clinical post-doctoral scientist, MRC Radiation & Genome Stability Unit
- 1994 - 1995 Non clinical post-doctoral scientist, MRC Radiobiology Unit
- 1991 - 1994 Post doctoral research assistant, Dept. of Physics, Queen Mary & Westfield College, University of London
Awards Training and Qualifications
- 2009, MIPEM, The Institute of Physics and Engineering in Medicine
- 2008, CRadP, Society for Radiological Protection
- 2004, MSRP, Society for Radiological Protection
- 1992, Cphys, MinstP, Institute of Physics
- 1987, PhD, Radiation Physics, University of London
- 1986, MSc in Radiation Physics, St Bartholomew'sMedical College, University of London
- 1983, BSc (Hons), Nottingham University
T.S.A. Underwood, H.C. Winter, M.A. Hill, J.D. Fenwick, Detector density and small field dosimetry: Integral versus point dose measurement schemes. Med. Phys. In press (2013)
E.M. O’Brien, J.M. Senra, S. Anbalagan, M.A. Hill, E.M. Hammond, Impact of Wee1 inhibition on the hypoxia-induced DNA damage response. Tumor Microenvironment and Therapy. 1, 37-45 (2013)
M. Themis, E. Garimberti, M.A. Hill and R.M. Anderson, Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET gamma-rays and high-LET alpha-particles. Int. J. Radiat. Biol. In press (2013) [PMID: 23679558]
H.A. Foster, G. Estrada-Girona, M. Themis, E. Garimberti, M.A. Hill, J.M. Bridger and R.M. Anderson, Relative proximity of chromosome territories influences chromosome exchange partners in radiation-induced chromosome rearrangements in primary human bronchial epithelial cells. Mut. Res. In press (2013) [PMID: 23791770]
K.J. Peach, M. Aslaninejad, R.J. Barlow, C.D. Beard, N. Bliss, J.H. Cobb, M.J. Easton, T.R. Edgecock, R. Fenning, I.S.K. Gardner, M.A. Hill, H.L. Owen, C.J. Johnstone, B. Jones, T. Jones, D.J. Kelliher, A. Khan, S. Machida, P.A. McIntosh, S. Pattalwar, J. Pasternak, J. Pozimski, C.R. Prior, J. Rochford, C.T. Rogers, R. Seviour, S.L. Sheehy, S.L. Smith, J. Strachan, S. Tygier, B. Vojnovic, P. Wilson, H. Witte, and T. Yokoi Conceptual design of a nonscaling fixed field alternating gradient accelerator for protons and carbon ions for charged particle therapy. Phys. Rev. ST Accel. Beams 16, 030101-34 (2013) [WOS: 000316174000001]
P. Reynolds, J.A. Anderson, J.V. Harper, M.A. Hill, S.W. Botchway, A.W. Parker and P. O'Neill, The dynamics of Ku70/80 and DNA-PKcs at DSBs induced by ionizing radiation is dependent on the complexity of damage. Nucleic Acids Res. 40, 10821-31 (2012) [PMID: 23012265]
G.B. Curwen, E.J.Tawn, K.K. Cadwell, L. Guyatt, J. Thompson and M.A. Hill, mFISH Analysis of Chromosome Aberrations Induced In Vitro by α-Particle Radiation: Examination of Dose-Response Relationships, Radiat. Res. 178, 414-424 (2012) [PMID: 23083107]
P. Wilson, B. Jones, T. Yokoi, M. Hill, B. Vojnovic, Revisiting the ultra-high dose rate effect: implications for charged particle radiotherapy using protons and light ions. Br J Radiol. 85, e933-939 (2012). [PMID: 22496068]
S. Anbalagan, I.M. Pires, C. Blick, M.A. Hill, D.J.P. Ferguson, D.A. Chan and E.M. Hammond, Radiosensitization of Renal Cell Carcinoma in vitro through the induction of autophagy, Radiotherapy and Oncology, 103, 388–393 (2012) [PMID: 22551566]
V. Kersemans, J. Thompson, B. Cornelissen, M. Woodcock, P.D. Allen, N. Buls, R.J. Muschel, M.A. Hill and S.C. Smart, Micro-CT for Anatomic Referencing in PET and SPECT: Radiation Dose, Biologic Damage, and Image Quality. . J Nucl Med. 52, 1827-33 (2011) [PMID: 21984798]
A.B. Abdelrazzak, D. L. Stevens, G. Bauer, P. O’Neill and M.A. Hill, The role of radiation quality in the stimulation of intercellular induction of apoptosis in transformed cells at very low doses, Radiat. Res.176, 346355 (2011) [PMID: 21663396]
B. Cornelissen, V. Kersemans, S. Darbar, J. Thompson, K. Shah, K. Sleeth, M.A. Hill, and K. Vallis, Imaging DNA damage in vivo using γH2AX-targeted immunoconjugates, Cancer Res. 71, 4539-4549 (2011) [PMID: 21586614]
M.A. Hill, C.S. Griffin, E.L. Pyke and D.L. Stevens, Chromosome aberration induction is dependent on the spatial distribution of energy deposition through a cell nucleus, Radiat. Prot. Dosim. 143, 172-176 (2011) [PMID: 21183544]
A.B. Abdelrazzak, P. O’Neill and M.A. Hill, Intercellular induction of apoptosis signalling pathways, Radiat. Prot. Dosim. 143, 289-293 (2011) [PMID: 21113059]
C. Bauerschmidt, M. Woodcock, D.L Stevens, M.A. Hill, K. Rothkamm and T. Helleday, Cohesin Phosphorylation and mobility of SMC1 at ionizing radiation induced DNA double strand breaks in human cells, Exp. Cell Res. 317, 330-337 (2011) [PMID: 21056556]
A.T. Natarajan, F. Palitti, M.A. Hill, D.L. Stevens and G. Ahnström, Influence of DMSO on Carbon-K ultrasoft X-rays induced chromosome aberrations in V79 Chinese hamster cells. Mut. Res., 691, 23-26 (2010) [PMID: 20600168]
C.E. Tambini, K.G. Spink, C.J. Ross, M.A. Hill and J. Thacker, The importance of xrcc2 in rad51-relate DNA damage repair, DNA Repair 9, 517-525 [PMID: 20189471]
M.-A. Hervé du Penhoat§, A. Eschenbrenner, F. Abel, A. Boissière, J.-M Guigner, A. Chetioui, M.-F. Politis, A. Touati, E. Sage, T.J. Jenner, D.L. Stevens, M.A. Hill, Double-strand break induction and repair in V79-4 hamster cells: the role of core ionizations, as probed by ultrasoft X-rays, Int. J. Radiat. Biol. 86, 205-219 (2010) [PMID: 20201649]
C. Bauerschmidt, C. Arrichiello, S. Burdak-Rothkamm,M. Woodcock, M.A. Hill, D.L. Stevens and K. Rothkamm, Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin, Nucleic Acids Research, 38, 477-487 (2010) [PMID: 19906707]
S. Badie, C. Liao, M. Thanasoula, P. Barber, M.A. Hill and M. Tarsounas, RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation, J. Cell Biol. 185, 587-600 (2009) [PMID: 19451272]
B. Phoenix, D. Green, M.A. Hill, B. Jones, A. Mill, D.L. Stevens Do the various radiations present in BNCT act synergistically? Cell survival experiments in mixed alpha-particle and gamma-ray fields, Applied Radiation and Isotopes, 67, S318-S320 (2009) [PMID: 19376715]
S.M. Moyes, E.M. Killick, J.F. Morris, M.A. Kadhim, M.A. Hill and K.E. Carr Changes produced by external radiation in parameters influencing intestinal permeability and microparticle uptake in vitro, Int. J. Radiat. Biol., 84, 467-486 (2008) [PMID: 18470746]
D.I. Portess, G. Bauer, M.A. Hill and P. O’Neill Low dose irradiation of non-transformed cells stimulates the selective removal of pre-cancerous cells via intercellular induction of apoptosis, Cancer Res., 67, 1246-1253 (2007). [PMID: 17283161]
R.M. Anderson, D.L. Stevens, N.D. Sumption, K.M.S. Townsend, D.T. Goodhead and M.A. Hill, Effect of linear energy transfer (LET) on complexity of -particle-induced chromosome aberrations in human CD34+ cells, Radiat. Res. 167, 541-550 (2007). [PMID: 1747795]
Reports from working groups
IARC (2012) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol 100D, A Review of Human Carcinogens. D. Radiation, Lyon, IARC Press. [PMID: 23189752]
AGIR (2007), Review of risks from tritium, report of the independent Advisory Group on Ionising Radiation.
Documents of the Health Protection Agency Radiation, Chemical and Environmental Hazards November 2007
IARC (2001) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol 78, Ionizing Radiation: part II: Internal Sources, Lyon, IARC Press. [PMID: 11421248]