Mammalian cells loaded with platinum-containing molecules are sensitized to fast atomic ions.
OBJECTIVE
This work investigates whether a synergy in cell death induction exists in combining atomic ions irradiation and addition of platinum salts. Such a synergy could be of interest in view of new cancer therapy protocol based on atomic ions--hadrontherapy--with the addition of radiosensitizing agents containing high-Z atoms. The experiment consists in irradiating by fast ions cultured cells previously exposed to dichloroterpyridine Platinum (PtTC) and analyzing cell survival by a colony-forming assay.


METHODS
Chinese Hamster Ovary (CHO) cells were incubated for six hours in medium containing 350 microM PtTC, and then irradiated by fast ions C(6+) and He(2+), with Linear Energy Transfer (LET) within range 2-70 keV/microm. In some experiments, dimethyl sulfoxide (DMSO) was added to investigate the role of free radicals. The intracellular localization of platinum was determined by Nano Secondary Ion Mass Spectroscopy (Nano-SIMS).


RESULTS
For all LET examined, cell death rate is largely enhanced when irradiating in presence of PtTC. At fixed irradiation dose, cell death rate increases with increasing LET, while the platinum relative effect is larger at low LET.


CONCLUSIONS
This finding suggests that hadrontherapy or protontherapy therapeutic index could be improved by combining irradiation procedure with concomitant chemotherapy protocols using platinum salts.
Usami
N
N
Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization, Oho, Tsukuba, Japan.
Furusawa
Y
Y
Kobayashi
K
K
Lacombe
S
S
Reynaud-Angelin
A
A
Sage
E
E
Wu
Ting-Di
TD
Croisy
A
A
Guerquin-Kern
J-L
JL
Le Sech
C
C
D000818:Animals; D016466:CHO Cells; D002244:Carbon; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D020450:Heavy Ions; D006371:Helium; D018499:Linear Energy Transfer; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000528:radiation effects / Q000627:therapeutic use; D011829:Radiation Dosage; D011836:Radiation Tolerance; D018629:Spectrometry, Mass, Secondary Ion; D013997:Time Factors
D005609:Free Radicals; D009944:Organoplatinum Compounds; D006371:Helium; D002244:Carbon; D004121:Dimethyl Sulfoxide