An alternative mechanism for radioprotection by dimethyl sulfoxide; possible facilitation of DNA double-strand break repair.
The radioprotective effects of dimethyl sulfoxide (DMSO) have been known for many years, and the suppression of hydroxyl (OH) radicals induced by ionizing radiation has been thought to be the main cause of this effect. However, the DMSO concentration used was very high, and might be toxic, in earlier studies. In the present study, we administered a lower, non-toxic concentration (0.5%, i.e., 64 mM) of DMSO before irradiation and examined its radioprotective effects. Colony formation assay and micronucleus assay showed significant radioprotective effects in CHO, but not in xrs5, which is defective in the repair function of DNA double-strand breaks. The levels of phosphorylated H2AX and the formation of 53BP1 foci 15 minutes after irradiation, which might reflect initial DNA double-strand breaks, in DMSO-treated CHO cells were similar to those in non-treated cells, suggesting that the radioprotective effects were not attributable to the suppression of general indirect action in the lower concentration of DMSO. On the other hand, 2 hours after irradiation, the average number of 53BP1 foci, which might reflect residual DNA double-strand breaks, was significantly decreased in DMSO-treated CHO cells compared to non-treated cells. The results indicated that low concentration of DMSO exerts radioprotective effects through the facilitation of DNA double-strand break repair rather than through the suppression of indirect action.
Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, Osaka, Japan. kashino@rri.kyoto-u.ac.jp
Genro
G
Kashino
Yong
Y
Liu
Minoru
M
Suzuki
Shin-ichiro
S
Masunaga
Yuko
Y
Kinashi
Koji
K
Ono
Keizo
K
Tano
Masami
M
Watanabe
D000818:Animals; D016466:CHO Cells; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism / Q000528:radiation effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000528:radiation effects; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D011837:Radiation-Protective Agents; D004121:Dimethyl Sulfoxide