Fast He2+ ion irradiation of DNA loaded with platinum-containing molecules.
OBJECTIVE
The association of radiotherapy and chemotherapy is an attractive approach to improve the therapeutic index of the treatment of tumors. A lot of work has been devoted to investigate the effects of X-ray, gamma-ray and neutron irradiation of DNA or living cells loaded with different chemical compounds containing heavy atoms like platinum. No such studies exist presently when fast atomic ions are chosen as ionizing particles. In the present work, we investigate quantitatively the increase of DNA breaks in complexes of plasmid-DNA loaded with platinum atoms under irradiation by fast atomic He2+ ions.


METHODS
DNA Plasmids (pBR322) are incubated in solutions containing different concentrations of terpyridine platinum (PtTC). In some preparations, dimethyl sulfoxide (DMSO), a free radical scavenger, has been added in order to investigate the role of the free radicals. The complexes of DNA plasmids loaded with high-Z atoms are irradiated under atmospheric conditions by He2+ ions at an energy of 143 MeV/amu and a linear energy transfert (LET) of 2.24 keV/microm. Analysis of DNA damage--single and double strand breaks--is made by electrophoresis on agarose gels.


RESULTS
The results show a significant increase in DNA strand breaks when platinum is present, indicating a radiosensitization by the high Z atoms. The increase in DNA damages is attributed to inner-shell ionization of a platinum atom by secondary electrons emitted along the He2+ tracks followed by an Auger deexcitation, leading, thus, to a local amplification of the radiative effects close to the DNA. The contributions of scavengeable--solvant mediated--indirect effects and non-scavengeable effects (direct ionization) are quantitatively evaluated.


CONCLUSIONS
Enhancement of DNA breaks in plasmids loaded with heavy atoms like platinum and irradiated by atomic ions are observed. This finding suggests an enhancement of cell death rate will occur under irradiation by atomic ions when the cells contain high-Z atoms located close to DNA due to the increase of the DNA breaks.
Usami
N
N
Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization, Oho, Tsukuba, Ibaraki, Japan.
Furusawa
Y
Y
Kobayashi
K
K
Frohlich
H
H
Lacombe
S
S
Le Sech
C
C
D016923:Cell Death; D004249:DNA Damage / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D016166:Free Radical Scavengers; D006371:Helium; D007477:Ions; D010957:Plasmids; D010984:Platinum / Q000737:chemistry*; D011836:Radiation Tolerance
D016166:Free Radical Scavengers; D007477:Ions; D006371:Helium; D010984:Platinum