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Cisplatin Radiosensitization of DNA Irradiated with 2ā20 eV Electrons: Role of Transient Anions
Platinum chemotherapeutic agents,
such as cisplatin (<i>cis</i>-diamminedichloroplatinumĀ(II)),
can act as radiosensitizers when
bound covalently to nuclear DNA in cancer cells. This radiosensitization
is largely due to an increase in DNA damage induced by low-energy
secondary electrons, produced in large quantities by high-energy radiation.
We report the yields of single- and double-strand breaks (SSB and
DSB) and interduplex cross-links (CL) induced by electrons of 1.6ā19.6
eV (i.e., the yield functions) incident on 5 monolayer (ML) films
of cisplatināDNA complexes. These yield functions are compared
with those previously recorded with 5 ML films of unmodified plasmid
DNA. Binding of five cisplatin molecules to plasmid DNA (3197 base
pairs) enhances SSB, DSB, and CL by factors varying, from 1.2 to 2.8,
1.4 to 3.5, and 1.2 to 2.7, respectively, depending on electron energy.
All yield functions exhibit structures around 5 and 10 eV that can
be attributed to enhancement of bond scission, via the initial formation
of core-excited resonances associated with Ļ ā Ļ*
transitions of the bases. This increase in damage is interpreted as
arising from a modification of the parameters of the corresponding
transient anions already present in nonmodified DNA, particularly
those influencing molecular dissociation. Two additional resonances,
specific to cisplatin-modified DNA, are formed at 13.6 and 17.6 eV
in the yield function of SSB. Furthermore, cisplatin binding causes
the induction of DSB by electrons of 1.6ā3.6 eV, i.e., in an
energy region where a DSB cannot be produced by a single electron
in pure DNA. Breaking two bonds with a subexcitation-energy electron
is tentatively explained by a charge delocalization mechanism, where
a single electron occupies simultaneously two Ļ* bonds linking
the Pt atom to guanine bases on opposite strands