Department of Biophysics, Panjab University, Chandigarh.
J Environ Pathol Toxicol Oncol. 2009;28(4):351-9. doi: 10.1615/jenvironpatholtoxicoloncol.v28.i4.90.
The aim of the present work was to gain insight into the putative anticancer effect of dietary zinc during 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. The rats were segregated into four groups, namely, normal control, DMH-treated, zinc-treated, and (DMH + zinc)-treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 12 weeks. Zinc in the form of zinc sulfate was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of the study. The effects of different treatments were studied on lipid peroxidation (LPO), reduced glutathione (GSH), and antioxidative enzymes, which included superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), as well as on the histoarchitecture of the colon. A total of 12 weeks of DMH treatment resulted in a significant increase in LPO. GSH levels and the activities of SOD, CAT, and GST were found to be significantly decreased following DMH treatment. A significant elevation in the activity of GR was observed following 12 weeks of DMH treatment. Histopathological studies showed well-differentiated signs of dysplasia, which included nuclei enlargement, epithelial thickening, and nuclear pleomorphism indicative of promotional phase of colon carcinogenesis in DMH-administered rats. Administration of zinc to DMH-treated rats decreased the levels of LPO and GSH significantly, but the activities of SOD and CAT were found to be significantly increased following zinc treatment. Zinc supplementation along with DMH treatment did not reveal any significant change in the activity of GR but significantly improved the activity of GST, which was depressed following DMH treatment. Also, zinc treatment in DMH-treated rats showed signs of great improvement, but structureless masses of the cells and hyperchromic nuclei were still visible occasionally. In conclusion, the results of this study suggest that zinc has a positive beneficial effect against chemically DMH-induced colonic preneoplastic progression in rats.
本研究旨在深入了解膳食锌在 1,2-二甲基肼（DMH）诱导的结肠癌发生过程中的潜在抗癌作用。将大鼠分为四组：正常对照组、DMH 处理组、锌处理组和（DMH+锌）处理组。每周通过皮下注射 DMH（30mg/kg 体重）诱导大鼠结肠癌发生，共 12 周。锌以硫酸锌的形式添加到大鼠饮用水中，剂量水平为 227mg/L，在整个研究期间自由摄取。研究了不同处理方法对脂质过氧化（LPO）、还原型谷胱甘肽（GSH）和抗氧化酶的影响，这些酶包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽 S-转移酶（GST）、谷胱甘肽还原酶（GR），以及对结肠组织学结构的影响。DMH 处理 12 周导致 LPO 显著增加。GSH 水平和 SOD、CAT 和 GST 的活性在 DMH 处理后显著降低。DMH 处理 12 周后，GR 的活性显著升高。组织病理学研究显示，DMH 给药大鼠出现了明显的分化不良迹象，包括核增大、上皮增厚和核多形性，提示处于结肠癌发生的促进阶段。给予锌可显著降低 DMH 处理大鼠的 LPO 和 GSH 水平，但锌处理后 SOD 和 CAT 的活性显著增加。锌补充与 DMH 处理同时进行并未导致 GR 活性发生显著变化，但显著改善了 GST 的活性，而 GST 的活性在 DMH 处理后受到抑制。此外，锌处理可使 DMH 处理大鼠的状况得到显著改善，但偶尔仍可见无结构的细胞团块和深染核。总之，本研究结果表明，锌对 DMH 诱导的大鼠结肠前癌变进展具有积极的有益作用。
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