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 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 (KBrO) solution (2 g/l) or tap water to BubR1 and wild-type (BubR1)mice for 16 weeks and examined the subsequent incidence of tumours.

Results: KBrO-treated BubR1 mice showed significantly higher mortality than the KBrO-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.