title: Induction of multinucleation in oral squamous cell carcinoma tissue with mutated p53 surviving boron neutron capture therapy.
abstract: OBJECTIVE
  To clarify the role of p53 in boron neutron capture therapy (BNCT) for oral squamous cell carcinoma (SCC), the effect of BNCT on oral SCC xenografts with either wild-type or mutant-type p53 was examined.
  
  
  METHODS
  Oral SCC cells expressing either wild-type (SAS/neo) or mutant-type p53 (SAS/mp53) were used to produce nude mouse tumours. Tumour-bearing mice received boronophenylalanine (BPA) at a dose of 250 mg/kg and tumours were exposed to neutron irradiation.
  
  
  RESULTS
  After BNCT, the growth of SAS/neo and SAS/mp53 tumours was suppressed remarkably and all tumours became undetectable within two weeks. However, three of six SAS/mp53 tumours showed regrowth in two months. Histological examination of BNCT-treated tumours revealed chromosomal condensation, micronucleation, nuclear segmentation and intra- and intercelluar vacuolation. Notably, multinucleated giant cells appeared in SAS/mp53 tumours early after BNCT, suggesting mitotic catastrophe. In SAS/mp53 tumours treated with BNCT, a rapid decrease in phosphorylated cell division cycle 2 (cdc2) and a high level of cyclin B1, required for premature mitosis, were observed.
  
  
  CONCLUSIONS
  These results indicate that BNCT suppressed oral SCC xenografts in nude mice efficiently, but cells survived in mutant-type p53 tumours. BNCT induces multinucleation which represents prestage of apoptosis or necrosis in oral SCC with mutant-type p53, but it may be also associated with the recurrence of BNCT-treated tumours.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Fujita
authors.forename: Naofumi
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kato
authors.forename: Soichi
authors.initials: S
authors.lastname: Iwai
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Ken
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yura
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016158:Genes, p53; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008938:Mitosis; D009062:Mouth Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D009154:Mutation; D009368:Neoplasm Transplantation; D010641:Phenotype; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; C033685:4-boronophenylalanine