Darel Hunting, Ph. D.
Development of Radiosensitizers Targeted to DNA
Radiotherapy is administered to 50-60% of cancer patients. Drugs which sensitize tumor cells to ionizing radiation are potentially a very effective means to improve radiotherapy. The investigator Hunting’s laboratory investigates radiosensitizers which target DNA, such as cisplatin, oxaliplatin and carboplatin. His research team has shown that the presence of cisplatin adducts in plasmid DNA greatly increases the formation of DNA double strand breaks by ionizing radiation (Radiation Research 179, 323-331 (2013)). This may be the mechanism by which cisplatin sensitizes cells to ionizing radiation.
Bromodeoxyuridine is a thymidine analog which is known to sensitize cells to ionizing radiation; however, the exact mechanism is not known. Doctor Hunting’s team demonstrated that the presence of bromodeoxyuridine does not radiosensitize double stranded DNA but greatly radiosensitizes single stranded bubbles within double stranded DNA. The presence of bromodeoxyuridine leads to the formation of DNA single strand breaks and interstrand crosslinks. (Radiation Research 162, 604-615 (2004); Biochemistry 44, 1932-1940 (2005); Mutation Research 704, 101-107 (2010).
- Boudaiffa, B., Cloutier, P., Hunting, D.J., Huels M.A. et Sanche, L. Resonant formation of DNA strand breaks by low energy (3-20 eV) electrons. Science 287, 1658-1660 (2000)
- Dextraze M.E., Cecchini S., Bergeron F., Girouard S., Turcotte K., Wagner J.R. et Hunting D.J. "Reaching for the other side: generating sequence-dependent interstrand cross-links with 5-bromodeoxyuridine and ?-rays". Biochemistry 48, 2005–2011 (2009)
- Gantchev T.G. & Hunting D.J. "Modeling the interactions of the nucleotide excision repair UvrA(2) dimer with DNA." Biochemistry 49, 10912-24 (2010)
- M. Rezaee, L. Sanche & D.J. Hunting. "Cisplatin enhances the formation of DNA single- and double-strand breaks by hydrated electrons and hydroxyl radicals". Radiation Research 179, 323-331 (2013)
Know-How & Opportunities for Collaboration
- DNA damage and repair
- Molecular modelling of DNA