Open AccessEffect of Electroporation on Cell Killing by Boron Neutron Capture Therapy Using Borocaptate Sodium ( 10 B‐BSH)
Author(s) -
Ono Koji,
Kinashi Yuko,
Masunaga Shinichiro,
Suzuki Minoru,
Takagaki Masao
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00533.x
Subject(s) - electroporation , radiochemistry , neutron capture , irradiation , boric acid , neutron temperature , chemistry , cell culture , boron , neutron , biochemistry , biology , physics , genetics , organic chemistry , quantum mechanics , gene , nuclear physics
The cell membrane permeability of 10 B‐enriched borocaptate sodium (BSH) and the extent to which BSH is accumulated in cells are controversial. To elucidate these points and to enhance the accumulation of BSH in cells, the effect of electroporation on boron neutron capture therapy (BNCT) using BSH was investigated. The first group of SCCVII tumor cells was incubated in culture medium with 10 B‐BSH or 10 B‐enriched boric acid, and exposed to neutrons from the heavy water facility of the Kyoto University Reactor. More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated with electroporation in combination with 10 B‐BSH, and thereafter the cells were irradiated with neutrons. The cell‐killing effect of BNCT was measured by colony formation assay. The surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell‐killing effect of NCT depending on 10 B concentration and the preincubation time of cells in the BSH‐containing culture medium. The electroporation of cells with BSH markedly enhanced the BNCT effect in comparison with that obtained with preincubation alone. The effect of BSH‐BNCT with electroporation was almost equal to that of BNCT using 10 B‐boric acid at the same 10 B concentration. The effect of BNCT on cells pretreated with BSH and electroporation was not reduced by repeated washing of the cells before neutron irradiation. Decrease of the effect of BSH‐BNCT plus electroporation with increase in the waiting time between the electroporation and the neutron irradiation could be explained in terms of the extent of cell growth during that time. These data suggest that BSH penetrates the cells slowly and remains after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH thus introduced stays in the cells and is not lost in spite of the intensive washing of the cells. Therefore, if electroporation is applied to tumors after BSH injection, 10 B would remain in the tumors but be cleared from normal tissues, and selective accumulation of 10 B in tumors will be achieved after an appropriate waiting time.