Research Network for Metals in Medicine

 

 

Dr Carolyn T. Dillon

BSc(Hons), PhD (Syd)

Position: Lecturer in Nanoscience and Nanotechnology

Affiliation: Electron Microscope Unit and School of Chemistry, University of Sydney

Postal Address:
Electron Microscope Unit
Building F09, Room LG13
University of Sydney, NSW 2006
AUSTRALIA

Phone: +61 (2) 9351 5322
Fax: +61 (2) 9351 7682
Email: C.Dillon@chem.usyd.edu.au
Webpage: http://www.chem.usyd.edu.au/about/staff_dillon.html


Research Profile

Dr Carolyn Dillon possesses laboratory PhD and post-doctoral experience in the areas of metal carcinogenesis (since 1991) and metal containing anti-inflammatory drugs (since 1998), wherein she is not only experienced in chemical synthesis and characterisation but also in a number of biological assays including in-vitro cell culture assays (greater than 13 yrs experience) and animal assays (greater than 10 years experience). As part of her work she has been heavily involved in the development and use of X-ray microprobe analysis for determination of cell and tissue targets of drugs and carcinogens.

Dr Carolyn Dillon’s expertise has been recognised by invitations to present seminars at national synchrotron workshops. These include the: Australian Synchrotron Radiation Program, ANSTO, September, 1999; “Spectroscopic Applications of Synchrotron Radiation in Chemistry and Biology”, University of Sydney, November, 2000; Third ASRP Users Meeting, Monash University, February, 2002 and the Australian Synchrotron Environmental Workshop, October, 2002. Dr Carolyn Dillon was also invited to present this work in the new instruments and techniques session at the Royal Australian Chemical Institute conference in Inorganic Chemistry (IC-03) held in Feb, 2003. Dr Carolyn Dillon was the recipient of a young scientist award covering registration at the International Conference on Biological Inorganic Chemistry Conference in Florence, 2001 where a poster was presented on this work. The X-ray microprobe work was also accepted for an oral presentation at the X-ray microscopy conference (XRM2002) at Grenoble in July, 2002. The microprobe work on metal-containing anti-inflammatory drugs was presented MEPSA Conference, University of Sydney, November, 2001 following an invitation from the organizing committee.

Dr Carolyn Dillon has written 4 successful ASRP grants as the Chief Investigator to perform SRIXE experiments (for investigations of the uptake and metabolism of metal-containing anti-inflammatory drugs) and has contributed to a further 3 ASRP grants as a partner investigator. Dr Carolyn Dillon has also submitted a successful grant as a CI, which will be performed in July 2003. The total funding received for these projects exceeds $50,000 for travel, and instrument time valued at US$230,000 (figure provided by Dr R. Garrett, ASRP). Dr Carolyn Dillon is actively involved in the Australian microprobe users group providing input into the development of the microprobe beam-line for the Australian Synchrotron (Boomerang 20).

Further to this Dr Carolyn Dillon is one of three co-directors for the Centre of Structural Biology and Structural Chemistry based at the University of Sydney.

Dr Carolyn Dillon was the first researcher to use microprobe PIXE, SRIXE and XAS for studying the spatial distribution and intracellular biotransformation products of the carcinogen, Cr(VI). This involved the development of sample preparative methods that resulted in high quality samples which were essential for obtaining meaningful results. The analyses have provided unprecedented information regarding the intracellular distributions and the chemistry that ensues when carcinogenic Cr(VI) and mutagenic Cr(V) complexes enter mammalian cells. Through microprobe PIXE and SRIXE experiments, Dr Carolyn Dillon was the first to show that highly active Cr(V) complexes could enter cells. Correlation of this data with genotoxicity data indicated that Cr(V) species were equally, if not more damaging than Cr(VI) species, suggesting a crucial role for Cr(V) in Cr(VI)-induced cancers. Micro-XAS analysis of cellular Cr also showed that Cr(VI) and Cr(V) species were reduced intracellularly to produce ultimate Cr(III) species. This work was highly innovative as it utilised, for the first time, the only spectroscopic technique capable of distinguishing all Cr oxidation states. The work has been published in high impact international journals.

Dr Carolyn Dillon’s contributions have also been pivotal in the development of micro-X-ray spectroscopy for research projects concerning metal containing anti-inflammatory drugs, Pt anti-cancer drugs and studies of endogenous (and expressed) proteins for studies of immuno-response. Specifically, microprobe (SRIXE and XAS) studies of the cellular uptake of metal containing anti-inflammatory drugs indicated dissociation of the metal and the parent ligand during uptake and cellular metabolism. Cellular distribution studies showed that the ligand (anti-inflammatory drug) localised at the nuclear membrane, where it is most likely targeting the COX enzyme associated with inflammation. Similarly, studies of a number of potential Pt anti-cancer drugs provided information regarding the relative cellular uptake of the complexes while micro-XAS analysis was used to differentiate the intracellular species. These studies have been crucial to our understanding of drug metabolism and will assist in the creation of more powerful drugs.


Selected Publications

Journal Articles (1998-2003)

  1. Dillon, C. T.; Lay, P. A.; Bonin, A. M.; Legge, G. J. F.; Cholewa, M.; Collins, T. J.; Kostka, K. L. The permeability, cytotoxicity and genotoxicity of Cr(V) and Cr(VI) complexes in V79 Chinese hamster lung cells. Chem. Res. Toxicol. 1998, 11, 119-129.
  2. Balaic, D. X.; Barnea, Z.; Varghese, J. N., Cholewa, M.; Dillon, C. T.; Lay, P.A.; Shea-McCarthy, G. Tapered monocapillary optics for synchrotron X-ray microfocusing. Proc. SPIE, 1998, 3449, 157-164.
  3. Dillon, C. T.; Lay, P. A.; Bonin, A. M.; Dixon, N. E.; Sulfab, Y. DNA interactions and bacterial mutagenicity of some Cr(III) imine complexes and their Cr(V) analogs. Evidence for Cr(V) intermediates in the genotoxicity of Cr(III). Aust J. Chem., 2000, 53, 411-424.
  4. Dillon, C. T.; Lay, P. A.; Bonin, A. M.; Cholewa, M. and Legge, G. J. F. Permeability, cytotoxicity and genotoxicity of Cr(III) complexes and some Cr(V) analogs in V79 Chinese hamster lung cells. Chem. Res. Toxicol. 2000, 13, 742-748.
  5. Cholewa, M.; Dillon, C. T.; Lay, P.A.; Phillips, D.; Talarico, T.; Lai, B. High Resolution Nuclear and X-ray microprobes and their applications in single cell analysis. Nucl. Instrum. & Meth. Phys. Res. B. 2001, 181, 715-722.
  6. Dillon, C. T.; Lay, P. A.; Kennedy, B. J.; Stampfl, A. P. J.; Cai, Z.; Ilinski, P.; Rodrigues, W.; Legnini, D. G., Lai, B. and Maser, J. Hard X-ray microprobe studies of chromium(VI)-treated V79 Chinese hamster lung cells: intracellular mapping of the biotransformation products of a chromium carcinogen. J. Biol. Inorg. Chem. 2002, 7, 640-645.
  7. Dillon, C. T.; Hambley, T. W.; Kennedy, B. J.; Lay, P. A.; Zhou, Q.; Davies, N. M.; Biffin, J. R. and Regtop, H. L. Gastrointestinal damage, anti-inflammatory activity and superoxide dismutase activity of copper and zinc complexes of the anti-inflammatory drug, indomethacin. Chem. Res. Toxicol. 2003, 16, 28-37.
  8. Dillon, C. T.; Kennedy, B. J.; Lay, P. A.; Lai, B.; Cai, Z.; Stampfl, A. P. J.; Ilinski, P.; Legnini, D. G.; Maser, J.; Rodrigues, W.; Shea-McCarthy, G.; Cholewa, M. Implementation of X-ray microscopy and micro-XANES analysis for investigations of the cellular uptake and cellular metabolism of transition metals. J. Physique IV, 2003, 104, 293-296.
  9. Hall, M. D.; Dillon, C. T.; Zhang, M.; Beale, P.; Cai, Z.; Lai, B.; Stampfl, A. P. J.; Hambley, T. W. The Cellular Distribution and Oxidation State of Platinum(II) and Platinum(IV) Antitumour Complexes in Cancer Cells. J. Biol. Inorg. Chem., 2003, 8, 726-732.
  10. Reviews and Book Chapters

  11. Codd, R.; Dillon, C. T.; Levina, A. and Lay, P. A. Studies on the genotoxicity of chromium: from the test tube to the cell. Coord. Chem. Rev. 2001, 216-217, 537-582.
  12. Weder, J.; Dillon, C. T.; Hambley, T. W.; Kennedy, B. J.; Lay, P. A.; Biffin, J. R.; Regtop, H. L.; Davies, N. M. Copper complexes of non-steroidal anti-inflammatory drugs: an opportunity yet to be realized. Coord. Chem. Rev., 2002, 232, 95-126.
  13. Levina, A.; Codd, R.; Dillon, C. T.; Lay, P. A. Chromium in biology: nutritional aspects and toxicology. Prog. Inorg. Chem., 2003, 51, Chapter 2, 145-250.
  14. Dillon, C. T.; Hambley, T. W.; Kennedy, B. J.; Lay, P. A.; Weder, J. E.; Zhou, Q. Copper and zinc complexes as anti-inflammatory drugs. in Metals in Biological Systems, Volume 41, Metal ions and their complexes in medication. Sigel, A and Sigel, H. (eds) (in press).


Facilities

  • Transmission Electron Microscopes (7 TEM’s including the Phillips CM12, Phillips CM 120, Carl Zeiss 902, VG, FEGTEM). Scanning Electron Microscopes (4 SEM’s including the XL30, Philips 505, )
  • Confocal Microscopes, a multiphoton system with a mira verdi laser system capable of spectral detection through the scanhead (to 4 PMTS) as well as transmission and reflection external detectors (4 PMTS) it can also do conventional 1 photon confocal microscopy with an 4 line argon laser, 543 He Ne and a 633 He Ne. The multiphoton system has a heated stage and flow through system and is capable of doing FRET. A Radiance 2000 with the same lasers but detection with the conventional filter system (3 PMTS and one transmission detector). A MRC600 with an argon/krypton laser (2 PMTS). We have received a grant to buy a new confocal system with which we will be able to do FLIM.
  • The EMU also boasts well equipped specimen preparation laboratories, highly experienced technical staff and a cell culture laboratory equipped with a biohazard cabinet and a cytotoxic cabinet for testing of potential anti-cancer and anti-inflammatory drugs.


International Linkages

Dr Carolyn Dillon possesses international links with the Advance Photon Source, Chicago.