[The biological effect of the phosphatidylinositol 3-kinase wortmannin following thermal neutron irradiation].
OBJECTIVE
Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to inhibit DNA-dependent protein kinase (DNA-PKcs) and to be an efficient radiosensitizer. We investigated the radiosensitizing effect of wortmannin on cell killing by thermal neutrons and the occurrence of mutations at the HPRT locus of CHO cells.


METHODS
Wortmannin was added to cells at a final concentration of 20 microM two hours before irradiation. Cells were irradiated with thermal neutrons. The biological end point of cell survival was measured by colony formation assay. Mutagenicity was calculated from the mutation frequency at the HPRT locus.


RESULTS
Wortmannin promoted cell death following thermal neutron irradiation especially in the absence of boron. However, mutagenicity was decreased by the wortmannin treatment.


CONCLUSIONS
Our results suggest that the inhibition of DNA-PKcs by wortmannin would be an effective radiosensitizer for BNCT and might bring about a reduction in the frequency of mutation by blocking the mis-joining of DNA damage during the repair process.
Research Reactor Institute, Kyoto University.
Yuko
Y
Kinashi
Shinichiro
S
Masunaga
Minoru
M
Suzuki
Kenji
K
Nagata
Koji
K
Ono
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D016754:Boron Neutron Capture Therapy; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D009154:Mutation / Q000187:drug effects / Q000528:radiation effects; D009502:Neutrons / Q000009:adverse effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011879:Radiotherapy Dosage; D000077191:Wortmannin
D000730:Androstadienes; D004268:DNA-Binding Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin