锌和铜补充剂对二甲基苯蒽诱导的大鼠致癌作用中尿 5-甲基-2'-脱氧胞苷预后价值的影响。

Effect of zinc and copper supplementation on the prognostic value of urinary 5-methyl-2'- deoxycytidine in DMBA-induced carcinogenesis in rats.

机构信息

Department of Bromatology, Medical University of Warsaw, Warsaw, Poland.

出版信息

Cancer Biomark. 2013 Jan 1;13(6):403-10. doi: 10.3233/CBM-130384.

DOI:10.3233/CBM-130384

PMID:24595076

Abstract

BACKGROUND

Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating events for cancer development.

OBJECTIVE

The aim of the present study was to assess the effect of zinc and copper on the DNA methylation in rats whose breast adenocarcinoma was simultaneously induced with 7, 12 dimethylbenz[a]anthracene (DMBA). The research focused on the kinetics of alterations in urinary 5-MedC (5-methyl-2'-deoxycytidine) at the early and late stages of carcinogenesis, as well as the influence of dietary factors on the process.

METHODS

The content of 5-methyl-2'-deoxycytidine in the rats' urine was determined by the ELISA (enzyme-linked immunosorbent assay) method. The 5-MedC level was standardized by conversion to the creatinine level.

RESULTS

It was found that in the rats fed only the standard diet and DMBA-treated the urinary levels of 5-MedC collected after the 10th week were considerably lower in comparison with the content of this biomarker in urine starting from the 19th week (43.56 ± 14.34 vs. 71.84 ± 42.64). The animals treated with DMBA and additionally obtaining copper were characterized by a much higher content of the examined biomarker in urine, both in the early phase of carcinogenesis (10th week) and later (19th week), as compared with the animals fed only the standard diet or the zinc-supplemented diet. In the rats with a fully developed tumor (100% incidence of the disease) the applied dose of resveratrol (0.2 mg/kg bw) was too low to prevent the intensive formation and increase of 5-MedC level in urine, additionally stimulated by the presence of Cu in the diet as well as by the active, ongoing neoplastic process.

CONCLUSIONS

Summing up the obtained results of investigations it can be said that the urinary level of 5-MedC depends on the applied supplementation.

摘要

背景

表观遗传改变已被确定为癌症预防策略的有希望的新靶点，因为它们发生在致癌作用的早期，并且代表癌症发展的潜在起始事件。

目的

本研究的目的是评估锌和铜对同时用 7,12-二甲基苯并[a]蒽（DMBA）诱导的大鼠乳腺腺癌的 DNA 甲基化的影响。该研究集中于在致癌作用的早期和晚期阶段，尿液中 5-MedC（5-甲基-2'-脱氧胞苷）的变化动力学，以及饮食因素对该过程的影响。

方法

采用 ELISA（酶联免疫吸附测定）法测定大鼠尿液中 5-甲基-2'-脱氧胞苷的含量。将 5-MedC 水平标准化为肌酐水平。

结果

发现仅喂食标准饮食和 DMBA 处理的大鼠，与从第 19 周开始尿液中此生物标志物的含量相比（43.56 ± 14.34 比 71.84 ± 42.64），第 10 周收集的尿液中 5-MedC 的水平明显较低。另外补充铜的 DMBA 处理的动物，在致癌作用的早期（第 10 周）和后期（第 19 周），尿液中被检查的生物标志物的含量均明显更高，与仅喂食标准饮食或补充锌的饮食的动物相比。在完全发展为肿瘤的大鼠（疾病发生率为 100%）中，应用的白藜芦醇剂量（0.2 mg/kg bw）太低，无法阻止饮食中存在的 Cu 以及活跃的、正在进行的肿瘤过程所引起的 5-MedC 水平的大量形成和增加。