This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu-BSA) or with fructose (Fru-BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML; 26.76 ± 1.09 nmol/mg BSA) levels in the Glu-BSA model. Nε-Carboxyethyllysine (CEL; 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1; 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru-BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu-BSA or Fru-BSA. Fructose treatment exerted a significant genotoxic dose-response effect including increases of BN with MNi (R2 = 0.7704; P = 0.0031), BN with NPBs (R2 = 0.9311; P < 0.0001) and BN with NBuds (R2 = 0.7118; P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400-600 µg/ml) induced DNA damage; however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo.

中文翻译：

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饮食糖和相关的内源性高级糖基化终产物会增加胞质阻滞微核细胞计数，从而增加WIL2-NS细胞中的染色体DNA损伤。

这项研究调查了葡萄糖和果糖以及晚期糖基化终产物（AGEs）对WIL2-NS细胞基因组损伤的影响，使用细胞分裂阻滞微核细胞仪（CBMN-Cyt）分析进行了测量。使用葡萄糖（Glu-BSA）或果糖（Fru-BSA）诱导的牛血清白蛋白（AGE-BSA）模型系统研究了AGEs的作用。液相色谱-质谱（LC-MS / MS）分析显示，Glu-BSA模型中的Nε-羧甲基赖氨酸（CML; 26.76±1.09 nmol / mg BSA）水平较高。在Fru-BSA模型中，Nε-羧乙基赖氨酸（CEL; 7.87±0.19 nmol / mg BSA）和甲基乙二醛衍生的氢咪唑酮1（MG-H1; 69.77±3.74 nmol / mg BSA）水平较高。使用CBMN-Cyt分析生物标记物[具有微核（MNi）的双核（BN）细胞，用葡萄糖，果糖，Glu-BSA或Fru-BSA处理9天后，带有核质桥的BN（NPB）和带有核芽的BN（NBuds）。果糖治疗具有显着的遗传毒性剂量反应作用，包括MNi增加BN（R2 = 0.7704; P = 0.0031），BNP增加NPB（R2 = 0.9311; P <0.0001）和BN增加NBuds（R2 = 0.7118; P = 0.0091 ）对细胞的影响，而葡萄糖对DNA的破坏作用则不太明显。高浓度的AGEs（400-600 µg / ml）引起DNA损伤；然而，对细胞毒性指数（坏死和凋亡）没有影响。总之，这项研究证明了生理上高浓度的还原糖或AGEs与染色体损伤的增加之间的潜在联系，这是糖尿病可能引起的病理学的重要新兴方面。最终，从长远来看，基因组完整性的丧失会加速衰老的速度并增加与年龄有关的疾病的风险。这些发现表明需要进一步研究糖基化对染色体不稳定性的影响，并确定这种作用是否能在人体内复制。