Physiol. Res. 52: 629-635, 2003

The Subcellular Targets of Mercaptoborate (BSH), a Carrier of 10B for Neutron Capture Therapy (BNCT) of Brain Tumors

 

V. Mareš1,2, D. Krajčí3, V. Lisá1

 

1Joint Laboratory of Cancer Cell Biology of the Institute of Physiology, Academy of Sciences and the First Faculty of Medicine, Charles University, Prague, 2Chair of Biology, Purkinje University, Ústí nad Labem, Czech Republic, 3Faculty of Medicine, Kuwait University, Department of Anatomy, Safat, Kuwait City, State of Kuwait

 

Received August 22, 2002

Accepted October 5, 2002


Summary
The transformed C6 glial cells in cultures were treated with sodium mercaptoborate (Na2B12H11SH, BSH), a carrier of atomic targets (10B) of thermal neutrons for the neutron capture therapy of brain tumors. As shown by light microscopy, the therapeutic dose of BSH (100 µg/ml) did not alter the gross morphology and growth of the population of cells within a 72 h treatment interval. Electron microscopic analysis of these cells revealed activation of nucleoli and, occasionally, enlarged and bifurcated mitochondria. After 200 µg BSH/ml and 72 h treatment, growth of the cell population was inhibited and ultrastructural changes became more profound. They included condensation of chromatin and its allocation to the nuclear envelope which formed deeper invaginations. Mitochondria further increased in size and were characterized by slim or angular cristae. Moreover, in circumscribed segments of some of the slightly swollen mitochondria their cristae disappeared or were reduced to fine pouch-like structures localized near the continuous outer membrane, suggestive for a non-destructive restructuring of the inner mitochondrial membrane. The smooth pinocytotic vesicles near the plasma membrane, lysosomes and heterogeneous dense bodies were more frequent. The revealed subcellular targets of BSH may initiate the development of pharmacological protocols aimed to further improve the tolerance to BSH by the healthy tissues of patients undergoing BNCT of brain tumors, e.g. by intervention into the oxidative stress triggered likely by the altered mitochondria.


Key words
Borocaptate (BSH) • Brain tumors • Mitochondria • Nucleus • Neutron Capture Therapy (NCT)


Reprint requests
V. Mareš, M.D., D.Sc., Institute of Physiology, Academy of Sciences, Vídeňská 1083, CZ-14200 Prague 4, Czech Republic. E-mail: maresv@biomed.cas.cz


© 2003 by the Institute of Physiology, Czech Academy of Sciences