Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model.
OBJECTIVE
Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue.


METHODS
Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1).


RESULTS
Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs


METHODS
55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration.


CONCLUSIONS
Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.
A
A
Monti Hughes
Department of Research and Production Reactors, National Atomic Energy Commission, Ezeiza, Province Buenos Aires, Argentina.
Ecc
E
Pozzi
Department of Instrumentation and Control, National Atomic Energy Commission, Ezeiza, Province Buenos Aires, Argentina.
S I
SI
Thorp
Department of Research and Production Reactors, National Atomic Energy Commission, Ezeiza, Province Buenos Aires, Argentina.
P
P
Curotto
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Laboratory of Cellular and Molecular Biology, School of Medical Sciences, Institute for Biomedical Research (BIOMED CONICET-UCA), Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.|National Research Council (CONICET), Buenos Aires, Argentina.
V A
VA
Medina
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Laboratory of Cellular and Molecular Biology, School of Medical Sciences, Institute for Biomedical Research (BIOMED CONICET-UCA), Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.
D J
DJ
Martinel Lamas
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
E S
ES
Rivera
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.
M A
MA
Garabalino
Department of Technology and Applications of Accelerators, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.
R O
RO
Farías
National Research Council (CONICET), Buenos Aires, Argentina.|Department of Technology and Applications of Accelerators, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.
S J
SJ
Gonzalez
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.
E M
EM
Heber
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.|Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
M E
ME
Itoiz
Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
R F
RF
Aromando
Idaho National Laboratory, Idaho Falls, ID, USA.
D W
DW
Nigg
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.|National Research Council (CONICET), Buenos Aires, Argentina.
V A
VA
Trivillin
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.|National Research Council (CONICET), Buenos Aires, Argentina.
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AE
Schwint
D000818:Animals; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects*; D006224:Cricetinae; D004195:Disease Models, Animal; D006632:Histamine / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D009062:Mouth Neoplasms / Q000532:radiotherapy*; D010879:Piperazines / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000532:radiotherapy*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*
D007211:Indoles; D010879:Piperazines; D011837:Radiation-Protective Agents; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D006632:Histamine
BNCT; boron neutron capture therapy; hamster cheek pouch precancer model; mucositis; oral cancer; radioprotector