Enhancement of sodium borocaptate (BSH) uptake by tumor cells induced by glutathione depletion and its radiobiological effect.
Sodium borocaptate (BSH) is widely used for boron neutron capture therapy (BNCT) of brain tumors. However, the mechanism of uptake by the tumor remains unclear. We investigated the sulfhydryl moiety of this compound. Down regulation of glutathione (GSH) by buthionine sulfoximine in cultured cells resulted in increase of BSH uptake (7.9-36.5%) compared to the control group and consequently the cytocidal effect of neutron irradiation also increased. On the other hand, the radiation caused damage by gamma-ray irradiation was suppressed when BSH uptake increased. These findings suggested that modulation of GSH enhanced the effect of B (n, alpha) reaction and the protective effect of secondary gamma-ray in BNCT.
Yoshida
Fumiyo
F
University of Tsukuba, Graduate School of Comprehensive Human Sciences, Functional and Regulatory Medical Sciences, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan. yoshi234@sakura.cc.tsukuba.ac.jp
Matsumura
Akira
A
Yamamoto
Tetsuya
T
Kumada
Hiroaki
H
Nakai
Kei
K
D000818:Animals; D001894:Borohydrides / Q000378:metabolism*; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy; D002478:Cells, Cultured; D006224:Cricetinae; D015536:Down-Regulation; D005720:Gamma Rays; D005910:Glioma / Q000378:metabolism* / Q000532:radiotherapy; D005978:Glutathione / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D012062:Relative Biological Effectiveness; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D001894:Borohydrides; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D019328:Buthionine Sulfoximine; D005978:Glutathione