BUBR1 insufficiency in mice increases their sensitivity to oxidative stress

Background/Aim: 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 (BubR1^L/L mice). Here, we examined the effect of low BUBR1 expression on oxidative stress-induced carcinogenesis in mice. Materials and Methods: We orally administered either a potassium bromate (KBrO₃) solution (2 g/l) or tap water to BubR1^L/L and wild-type (BubR1^+/+) mice for 16 weeks and examined the subsequent incidence of tumours. Results: KBrO₃-treated BubR1^L/L mice 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. Conclusion: Our results indicate that low BUBR1 expression increases oxidative stress-induced mortality in mice, possibly caused by splenic neoplasms.