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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Inhibition of diethylnitrosamine-induced rat liver chromosomal aberrations and DNA-strand breaks by synergistic supplementation of vanadium and 1α, 25-dihydroxyvitamin D_3
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Inhibition of diethylnitrosamine-induced rat liver chromosomal aberrations and DNA-strand breaks by synergistic supplementation of vanadium and 1α, 25-dihydroxyvitamin D_3

机译：协同补充钒和1α，25-二羟基维生素D_3抑制二乙基亚硝胺诱导的大鼠肝染色体畸变和DNA链断裂

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摘要

Vanadium (V) has recently been found to possess potent anti-neoplastic activity in rat hepatocarcinogenesis. Recent studies have suggested that the active metabolite of vitamin D_3, 1α,25-dihydroxyvitamin D_3 [1,25(OH)_2D_3], can inhibit growth and/or induce differentiation of a variety of cell types. In the present study, attempts have been made to investigate the combination effects on chromosomal aberrations (CAs) and DNA-strand breaks during the early preneoplastic stage of diethylnitrosamine (DEN)-induced rat liver carcinogenesis in male Sprague-Dawley rats. V (0.5 ppm ad libitum) and/or 1,25(OH)_2D_3 (0.3 μg/0.1 ml propylene glycol per os twice weekly) either alone or in combination were given to DEN-treated and control rats 4 weeks prior to DEN injection. Under these experimental conditions it was observed that, when given in combination, V and 1,25(OH)_2D_3 offered maximum protection against DEN-induced structural aberrations 96 h (66.7%, P<0.05), 15 days (44.9%. P<0.005) and 30 days (63.8%, P<0.001) after DEN injection. Synergistic supplementation of both V and 1,25(OH)_2D_34 weeks before DEN injection was found to offer significant (64.1%, P<0.001) protection against generation of single-strand breaks when compared with the DEN control. Thus, the combination effect of V, an essential trace element, and of 1,25(OH)_2D_3, a dietary micronutrient, appears beneficial in preventing genetic damage in liver cells upon alkylation induced by DEN.
机译：最近发现钒（V）在大鼠肝癌发生中具有有效的抗肿瘤活性。最近的研究表明，维生素D_3、1α，25-二羟基维生素D_3 [1,25（OH）_2D_3]的活性代谢产物可以抑制多种细胞的生长和/或诱导其分化。在本研究中，已经尝试研究在二乙基亚硝胺（DEN）诱导的雄性Sprague-Dawley大鼠肝癌发生的前肿瘤形成早期，其对染色体畸变（CAs）和DNA链断裂的联合作用。 DEN注射前4周，单独或联合使用V（0.5 ppm随意服用）和/或1,25（OH）_2D_3（0.3 mg / 0.1 ml丙二醇，每周一次，口服两次） 。在这些实验条件下，可以观察到，当V和1,25（OH）_2D_3组合使用时，可以最大程度地保护DEN诱导的96 h（66.7％，P <0.05），15天（44.9％。P） <0.005）和DEN注射后30天（63.8％，P <0.001）。与DEN对照相比，发现在DEN注射前V和1,25（OH）_2D_34的协同补充可提供显着（64.1％，P <0.001）的保护，防止单链断裂的产生。因此，必需的微量元素V和饮食中的微量营养元素1,25（OH）_2D_3的联合作用似乎对预防DEN诱导的烷基化对肝细胞的遗传损伤有好处。

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