Accumulation of boron-10 (10B) in cell cultures exposed to mercaptododecaborate (Na2H(11)10B12SH) used for the neutron capture therapy of brain tumors.
Toxicity of mercaptoundecahydro-closo-dodecaborate (MHB, Na2H(11)10B12SH) and accumulation of MHB-derived 10B were studied in E7 neuroblastoma, C6 glioma, HeLa cells and embryonic lung LEP 19 fibroblasts in culture in exponential and stationary phases of growth (2- and 7-day-old cultures, respectively). The pilot study of acute toxicity, performed on C6 glioma cells, showed good tolerance of the drug up to 1000 micrograms/ml (4.8 x 10(-3) M), when cell growth slowed and a small part of the population was lethally damaged (8.3%, 20-h incubation interval). The changes became more extensive and appeared sooner (toward 5 h) at 2000 micrograms MHB/ml (9.5 x 10(-3) M). None of the four cell lines used was found to be affected in gross morphology or growth by 200 micrograms MHB/ml within a 5-day culture interval. When exposed to this dose for 4 h, the amount of 10B accumulated in cell lines at the exponential growth phase ranged from 0.51 to 4.4 ng/micrograms protein; in the stationary cultures of the corresponding cell phenotype, the 10B values were 3 to 10 times lower (0.12-1.2 ng/micrograms protein). Irrespective of the growth phase, the values achieved in C6 glioma cells were several times higher than in the other cell lines. Furthermore, in the glioma cells, particularly in the exponential phase of growth, accumulation of 10B proceeded against the marked concentration gradient. The data provide a new indication for the use of MHB for boron neutron capture therapy of brain tumors.
Mares
V
V
Institute of Physiology, Czechoslovak Academy of Sciences, Prague.
Baudysová
M
M
Kvítek
J
J
Hnatovicz
V
V
Cervená
J
J
Vacík
J
J
Folbergrová
J
J
D000818:Animals; D001894:Borohydrides / Q000378:metabolism / Q000627:therapeutic use*; D001895:Boron / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D007554:Isotopes; D051379:Mice; D009502:Neutrons; D011882:Radiotherapy, High-Energy; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D001894:Borohydrides; D007554:Isotopes; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron