BUBR1 Insufficiency in Mice Increases their Sensitivity to Oxidative Stress.
OBJECTIVE
Budding uninhibited by benzimidazole-related 1 (BUBR1) plays an important role in the spindle assembly checkpoint to prevent chromosome missegregation and aneuploidy during mitosis. We previously generated mutant mice that express BUBR1 at only 20% of the normal level (BubR1L/Lmice). Here, we examined the effect of low BUBR1 expression on oxidative stress-induced carcinogenesis in mice.


METHODS
We orally administered either a potassium bromate (KBrO3) solution (2 g/l) or tap water to BubR1L/Land wild-type (BubR1+/+)mice for 16 weeks and examined the subsequent incidence of tumours.


RESULTS
KBrO3-treated BubR1L/Lmice showed significantly higher mortality than the KBrO3-treated BubR1+/+and control tap water-treated mice (p=0.0082). Histopathological and immunohistochemical analyses revealed that the spleens of surviving BubR1L/L mice were occupied by non-B-, non-T-cells with high proliferative potential.


CONCLUSIONS
Our results indicate that low BUBR1 expression increases oxidative stress-induced mortality in mice, possibly caused by splenic neoplasms.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Daisuke
D
Matsuda
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan maehara@surg2.med.kyushu-u.ac.jp takum@surg2.med.kyushu-u.ac.jp.
Takuya
T
Matsumoto
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kenichi
K
Honma
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ayae
A
Ikawa-Yoshida
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mitsuho
M
Onimaru
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tadashi
T
Furuyama
Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshimichi
Y
Nakatsu
Department of Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Teruhisa
T
Tsuzuki
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan maehara@surg2.med.kyushu-u.ac.jp takum@surg2.med.kyushu-u.ac.jp.
Yoshihiko
Y
Maehara
D000818:Animals; D001959:Bromates / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003839:Deoxyadenosines / Q000652:urine; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000378:metabolism
D001959:Bromates; C584278:Bub1b protein, mouse; D002273:Carcinogens; D018797:Cell Cycle Proteins; D003839:Deoxyadenosines; C019536:potassium bromate; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; D017346:Protein Serine-Threonine Kinases
KBrO3; Oxidative stress; aneuploidy; splenic neoplasms