Diet-induced obesity increases the frequency of Pig-a mutant erythrocytes in male C57BL/6J mice.
Diet-induced obesity increases the frequency of Pig-a mutant erythrocytes in male C57BL/6J mice.
复制标题
饮食引起的肥胖增加了雄性 C57BL/6J 小鼠中 Pig-a 突变红细胞的频率。
DOI：
10.1002/em.22058
复制
发表时间：
2016
影响因子：
2.8
通讯作者：
Wilson,MarkJ
中科院分区：
文献类型：
--
作者：
Wickliffe,JeffreyK;Dertinger,StephenD;Torous,DorotheaK;Avlasevich,SvetlanaL;Simon-Friedt,BridgetR;Wilson,MarkJ
Obesity increases the risk of a number of chronic diseases in humans including several cancers. Biological mechanisms responsible for such increased risks are not well understood at present. Increases in systemic inflammation and oxidative stress, endogenous production of mutagenic metabolites, altered signaling in proliferative pathways, and increased sensitivity to exogenous mutagens and carcinogens are some of the potential contributing factors. We hypothesize that obesity creates an endogenously mutagenic environment in addition to increasing the sensitivity to environmental mutagens. To test this hypothesis, we examined twoin vivogenotoxicity endpoints.Pig‐amutant frequencies and micronucleus frequencies were determined in blood cells in two independent experiments in 30‐week old male mice reared on either a high‐fat diet (60% calories from fat) that exhibit an obese phenotype or a normal‐fat diet (10% calories from fat) that do not exhibit an obese phenotype. Mice were assayed again at 52 weeks of age in one of the experiments.N‐ethyl‐N‐nitrosourea (ENU) was used as a positive mutation control in one experiment. ENU induced a robustPig‐amutant and micronucleus response in both phenotypes. Obese, otherwise untreated mice, did not differ from non‐obese mice with respect toPig‐amutant frequencies in reticulocytes or micronucleus frequencies. However, such mice, had significantly higher and sustainedPig‐amutant frequencies (increased 2.5‐3.7‐fold,p< 0.02) in erythrocytes as compared to non‐obese mice (based on measurements collected at 30 weeks or 30 and 52 weeks of age). This suggests that obesity, in the absence of exposure to an exogenous mutagen, is itself mutagenic. Environ. Mol. Mutagen. 57:668–677, 2016. © 2016 Wiley Periodicals, Inc.
