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高剂量膳食维生素B6对BALB/c小鼠肿瘤生长的抑制及免疫状态的增强作用

Suppression of tumor growth and enhancement of immune status with high levels of dietary vitamin B6 in BALB/c mice.

作者信息

Gridley D S, Stickney D R, Nutter R L, Slater J M, Shultz T D

出版信息

J Natl Cancer Inst. 1987 May;78(5):951-9.

PMID:3472003
Abstract

Effects of dietary vitamin B6 at levels ranging from deficiency to megadoses on the development of herpes simplex virus type 2-transformed (H238) cell-induced tumors and on in vitro responses relating to cell-mediated immunity were examined. Male BALB/cByJ mice (n = 260), 5 weeks of age, were fed 20% casein diets containing pyridoxine (PN) at 0.2, 1.2 for the control diet, 7.7, or 74.3 mg/kg diet for 4-11 weeks. After 4 weeks of dietary treatment, 120 of the mice received an injection of H238 cells; mice without H238 injection served as controls. At 4, 8, and 11 weeks, animals from each group were euthanized and blood and spleen samples obtained. Mice fed 0.2 mg PN developed mild deficiency symptoms and gained significantly less weight than those fed 1.2-, 7.7-, and 74.3-mg PN diets. Thirteen to 16 days after tumor cell injection, primary tumor incidence was lowest in mice fed 74.3 mg PN; later, incidence among groups was similar. Mice fed 1.2 mg PN had the largest primary tumor volume, the highest incidence of lung metastases, and the greatest number of metastatic nodules per animal at 7 weeks post injection. Overall, lower tumor volumes were found in animals fed 7.7 and 74.3 mg PN (14 and 32% less than the tumor volume for those fed 1.2 mg PN, respectively); mice fed 0.2 mg PN had the lowest tumor volume. Blood and spleen lymphoproliferative response to stimulation by phytohemagglutinin or concanavalin A generally tended to be higher in mice fed 7.7 and 74.3 mg PN as compared to that in animals fed either 0.2 or 1.2 mg PN. However, decreased mitogen-stimulated responsiveness was observed in all animals with progressive tumor growth. Tumor growth also resulted in splenomegaly and increased thymic atrophy. Significant negative relationships between tumor volume and tumor pyridoxal 5-phosphate (PLP) concentrations were observed for 1.2-, 7.7-, and 74.3-mg PN diet groups. These data suggest that high dietary intake of vitamin B6 may have suppressed tumor development by either immune enhancement or PLP growth regulation of this tumor.

摘要

研究了从缺乏到超大剂量范围内的膳食维生素B6对2型单纯疱疹病毒转化(H238)细胞诱导肿瘤的发展以及与细胞介导免疫相关的体外反应的影响。给260只5周龄的雄性BALB/cByJ小鼠喂食含0.2、1.2(对照饮食)、7.7或74.3 mg/kg饮食的吡哆醇(PN)的20%酪蛋白饮食,持续4 - 11周。经过4周的饮食处理后,120只小鼠注射H238细胞;未注射H238细胞的小鼠作为对照。在第4、8和11周,对每组动物实施安乐死并采集血液和脾脏样本。喂食0.2 mg PN的小鼠出现轻度缺乏症状,体重增加明显低于喂食1.2、7.7和74.3 mg PN饮食的小鼠。肿瘤细胞注射后13至16天,喂食74.3 mg PN的小鼠原发性肿瘤发生率最低;后来,各组之间的发生率相似。喂食1.2 mg PN的小鼠在注射后7周时原发性肿瘤体积最大,肺转移发生率最高,每只动物的转移结节数量最多。总体而言,喂食7.7和74.3 mg PN的动物肿瘤体积较小(分别比喂食1.2 mg PN的动物肿瘤体积小14%和32%);喂食0.2 mg PN的小鼠肿瘤体积最小。与喂食0.2或1.2 mg PN的动物相比,喂食7.7和74.3 mg PN的小鼠对植物血凝素或伴刀豆球蛋白A刺激的血液和脾脏淋巴细胞增殖反应总体上往往更高。然而,随着肿瘤的进展,在所有动物中均观察到有丝分裂原刺激的反应性降低。肿瘤生长还导致脾肿大和胸腺萎缩加剧。在1.2、7.7和74.3 mg PN饮食组中,观察到肿瘤体积与肿瘤磷酸吡哆醛(PLP)浓度之间存在显著的负相关关系。这些数据表明,高膳食摄入维生素B6可能通过增强免疫或对该肿瘤的PLP生长调节来抑制肿瘤发展。

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