Abstract The aim of the research was to compare the impact of nano- and micro-sized-zinc on the kinetics of changes in the level of 3-methyladenine, 7-methylguanine, 7-methylguanosine, O-methylguanosine, 1-methyladenosine, N6-methyl-2’-deoxyguanosine in urine of rats with breast cancer. Female Sprague-Dawley rats divided into 3 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano and micro-sized zinc particles. To induce the mammary cancer (adenocarcinoma), rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a validated high performance liquid chromatography coupled to mass spectrometry method. In the first stage of investigations a synergistic activity of nanosized Zn with DMBA on the growth of the neoplastic process was found. During that time a statistically significant increase in the levels of all six examined markers in the rats’ urine was observed. However, as the experiment continued, the supplementation with nanosized zinc caused inhibition of tumour growth, being followed by regression and remission of tumours, as well as, a statistically significant systematic reduction of the levels of methyl derivatives in the urine. Biopsy images indicated grade 1 tumours with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, moderately-differentiated grade 2 adenocarcinoma was identified. It was found that the biological activity of zinc depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.

中文翻译：

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纳米锌、表观遗传变化及其与 DMBA 诱发大鼠乳腺癌的关系

摘要 本研究的目的是比较纳米和微米级锌对 3-甲基腺嘌呤、7-甲基鸟嘌呤、7-甲基鸟苷、O-甲基鸟苷、1-甲基腺苷、N6 水平变化动力学的影响。乳腺癌大鼠尿液中的-甲基-2'-脱氧鸟苷。在研究中使用分为 3 组的雌性 Sprague-Dawley 大鼠。只给动物喂食对照饮食或补充有纳米和微米尺寸锌颗粒的饮食。为了诱发乳腺癌（腺癌），用7,12-二甲基苯并[a]蒽（DMBA）治疗大鼠。修饰的核苷通过经验证的高效液相色谱联用质谱法测定。在研究的第一阶段，发现纳米锌与 DMBA 对肿瘤生长过程的协同作用。在此期间，观察到大鼠尿液中所有六种检测标志物的水平在统计学上显着增加。然而，随着实验的继续，补充纳米级锌会抑制肿瘤生长，随后肿瘤消退和缓解，以及尿液中甲基衍生物水平的统计学显着系统降低。活检图像显示，在锌纳米颗粒治疗组中，1 级肿瘤具有多个炎症浸润，而在其他组中，发现了中度分化的 2 级腺癌。研究发现，锌的生物活性取决于应用颗粒的大小，因为锌微粒的治疗对癌症进展没有太大影响。