Inhibition of DNA-double strand break repair by antimony compounds.
DNA double strand breaks (DSBs), induced by gamma-irradiation in Chinese hamster ovary cells, were used to examine whether antimony compounds affect the repair of DNA damage. The cells were first incubated with antimony trichloride or antimony potassium tartrate (both Sb(III)) for 2 h, and then irradiated with gamma-rays at a dose of 40 Gy. The DNA DSB was quantified with pulsed field gel electrophoresis immediately after irradiation (non-repair group) as well as at 30 min post-irradiation (repair group). The degree of repair inhibition was determined by the differences in the amount of DNA DSB between non-repair and repair groups. Both antimony compounds inhibited repair of DNA DSB in a dose dependent manner. In trichloride, 0.2 mM antimony significantly inhibited the rejoining of DSB, while 0.4 mM was necessary in potassium antimony tartrate. The mean lethal doses, D(0), for the treatment with antimony trichloride and antimony potassium tartrate, were approximately 0.21 and 0.12 mM, respectively. This indicates that the repair inhibition by antimony trichloride occurred in the dose range near D(0), but the antimony potassium tartrate inhibited the repair at doses where most cells lost their proliferating ability. This is the first report to indicate that antimony compounds may inhibit the repair of radiation-induced DNA DSB.
Takahashi
Sentaro
S
Environmental and Toxicological Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, 263-8555, Chiba, Japan. sentaro@nirs.go.jp
Sato
Hiroshi
H
Kubota
Yoshihisa
Y
Utsumi
Hiroshi
H
Bedford
Joel S
JS
Okayasu
Ryuichi
R
D000818:Animals; D000965:Antimony / Q000494:pharmacology*; D000966:Antimony Potassium Tartrate / Q000494:pharmacology; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D005720:Gamma Rays
D004247:DNA; D000965:Antimony; D000966:Antimony Potassium Tartrate