Mutagenic effect of borocaptate sodium and boronophenylalanine in neutron capture therapy.
OBJECTIVE
To investigate the mutagenic effect in boron neutron capture therapy (BNCT), Chinese hamster ovary cells were incubated with 10 B-enriched borocaptate sodium (BSH) or para-boronophenylalanine (BPA) before exposure to thermal neutrons, and the occurrence of mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus was measured.


METHODS
BSH or BPA was added to cells 20 h or 2 h before irradiation and removed before irradiation. Cells were irradiated with thermal neutrons. The biologic end point of cell survival was measured by colony formation assay. The mutagenicity was calculated from the mutation frequency at the HPRT locus.


RESULTS
The mutagenicity of BSH and BPA was similar to that of 10B boric acid when the cells were irradiated with neutrons at an isosurvival dose after 2-h preincubation. Preincubation with BSH for 20 h, compared with preincubation for just 2 h, had no effect on either cytotoxicity or mutagenicity in BNCT. However, with BPA, 20-h preincubation, compared with 2-h preincubation, caused an increase in the cell killing effect, but a decrease in the mutagenic effect of the BNCT.


CONCLUSIONS
After 20-h incubation, BPA was less mutagenic than BSH. The mutagenic study of electroporated BPA or BSH revealed a reduced mutagenicity. These results suggest that the retention of these boron compounds in the cells causes a more accurate assault on the cell and lessens the chance of misrepair after neutron irradiation.
Kinashi
Yuko
Y
Research Reactor Institute, Kyoto University, Sennan-gun, Osaka, Japan. kinashi@rri.kyoto-u.ac.jp
Masunaga
Shin-ichiro
S
Ono
Koji
K
D000818:Animals; D001894:Borohydrides / Q000633:toxicity*; D001896:Boron Compounds / Q000633:toxicity*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects*; D016466:CHO Cells / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D009152:Mutagenicity Tests; D009154:Mutation; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000633:toxicity*
D001894:Borohydrides; D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; C033685:4-boronophenylalanine