Department of Biophysics, Panjab University, Chandigarh 160 014, India.
Oncol Res. 2009;18(1):17-23. doi: 10.3727/096504009789745665.
The present study evaluated the modulatory effects of zinc on colonic membrane fluidity and surface abnormalities following 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum, for the entire duration of the study. Brush border membranes (BBM) were isolated from the colon of rats and the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. The results demonstrated a significant increase in the polarization and anisotropy, accompanied by an increase in order parameter in the membrane preparations from the colon of DMH-injected rats. Further, studies with pyrene fluorophore indicated a marked decrease in membrane microviscosity following DMH treatment. However, the alterations in membrane fluorescence polarization and the fluidity parameters were completely restored following zinc treatment. Drastic alterations in colon surface were noticed after 8 weeks of DMH treatment. However, zinc treatment to DMH-treated rats greatly restored normalcy in the colonic surface. The study concludes that zinc has a strong membrane stabilizing effect and thus has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.
本研究评估了锌对 1,2-二甲基肼(DMH)诱导的结肠癌发生后结肠膜流动性和表面异常的调节作用。将大鼠分为四组:正常对照组、DMH 处理组、锌处理组、DMH+锌处理组。通过每周一次皮下注射 DMH(30mg/kg 体重)进行 8 周,引发结肠癌发生。锌(以硫酸锌的形式)以 227mg/L 的剂量水平添加到大鼠饮用水中,自由摄取,整个研究期间均如此。从大鼠结肠中分离出刷状缘膜(BBM),并使用膜外荧光探针 1,6-二苯基-1,3,5-己三烯(DPH)通过稳态荧光偏振技术评估流动性参数。通过将掺入膜中的芘的激基复合物形成来测量平动扩散。结果表明,DMH 注射大鼠结肠膜制剂的极化和各向异性显著增加,同时有序参数增加。此外,使用芘荧光探针的研究表明,DMH 处理后膜微粘度明显降低。然而,锌处理完全恢复了膜荧光偏振和流动性参数的变化。DMH 处理 8 周后,结肠表面发生剧烈变化。然而,锌处理可使 DMH 处理大鼠的结肠表面恢复正常。研究结论是,锌具有很强的膜稳定作用,因此对大鼠化学诱导的结肠前癌变进展具有积极的有益影响。