Molecular mechanism of the DNA sequence selectivity of 5-halo-2'-deoxyuridines as potential radiosensitizers.
The 5-halo-2'-deoxyuridines bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU) are well-known photosensitizers for inducing DNA/RNA-protein cross-linking and potential radiosensitizers for radiotherapy of cancer. The dependence of the photosensitivity of BrdU and IdU on the DNA sequence has been well-observed, but it is unknown whether there is a similar DNA sequence selectivity in their radiosensitivity. Here we show a new ultrafast electron transfer (UET) mechanism for the likely DNA sequence dependence of the radiosensitivity of BrdU and IdU. Our femtosecond time-resolved transient laser absorption spectroscopic measurements provide the first real-time observation of the UET reactions of BrdU/IdU with the anion states of adenine and guanine. It is shown that the UET between BrdU and dA*(-) (dA(-)) is more effective than that between BrdU and dG*(-). This is related to the recent observation that dG*(-) is highly destructive while dA(-) is long-lived. This mechanistic understanding may lead to the improvement of BrdU and IdU to achieve sufficient radiosensitizing efficacy and the development of more effective radiosensitizers for clinical uses.
Wang
Chun-Rong
CR
Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1.
Lu
Qing-Bin
QB
D001973:Bromodeoxyuridine / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D003857:Deoxyuridine / Q000737:chemistry*; D007700:Kinetics; D012313:RNA / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D012313:RNA; D004247:DNA; D001973:Bromodeoxyuridine; D003857:Deoxyuridine