应用转基因小鼠模型研究细小病毒非结构基因抗肿瘤作用

A STUDY ON THE ANTITUMORIGENESIS OF MVMNS GENE IN TRANSGENIC MICE

目的探讨小鼠细小病毒非结构基因转基因小鼠抗肿瘤的作用。方法给予肺组织表达非结构（ＮＳ）基因的首建者转基因小鼠Ａ６子代雄性鼠腹腔注射氨基甲酸乙酯水溶液，以诱发肺瘤结节。给予肩胛皮下不表达ＮＳ基因的Ａ６子代雌性鼠局部注射致癌剂３┐甲基胆蒽苯溶液，以诱发肩胛皮下肿瘤，另一部分子代雌性鼠腹腔接种Ｓ１８０肉瘤细胞２×１０６个／只，使之荷瘤。结果诱发携带ＮＳ基因组小鼠肺瘤结节平均数显著少于未携带ＮＳ基因组（Ｐ＜０．０１）。携带与未携带ＮＳ基因小鼠组的肩胛皮下肿瘤形成率、平均瘤重无显著差异（Ｐ＞０．０５）。腹腔接种Ｓ１８０肉瘤细胞小鼠，携带与未携带ＮＳ基因组的生命延长率无显著差异（Ｐ＞０．０５）。结论表达ＮＳ基因的组织具有抑制化学致癌剂致瘤形成的作用，而不表达ＮＳ基因的组织则无此作用，转基因小鼠对外源性肿瘤细胞的生长无抑制作用。ＮＳ基因可能主要在表达的细胞内发挥作用。

Objective:To study the antitumorigenesis of MVMNS transgenic mice.Methods:Urethan water solution was administered by intraperitoneal injection to induce lung tumor nodes in the male offspring of A6 transgenic mouse, in which the NS gene is expressed in the lung.3 methylcholanthrene benzol solution was administered by subcutaneous injection at left scapular region to induce tumor in the female offspring of A6,in which scapular NS gene was not expressed. S180 tumor cells were administered 2×10 6/mouse by intraperitoneal injection in other female offspring to load tumor cells.Results:In the group with intraperitoneal injection,the average lung tumor nodes in the group carrying NS gene were significantly lower than those of NS gene free mice( P <0.01).In the group with subcutaneous injection,the rate of tumor formation,the average tumor weight showed no difference between NS positive and negative mice.In the group with intraperitoneal injection of S180 tumor cells,the difference of prolongation of life between NS positive and negative mice were not significant( P >0.05).Conclusion:The tissues expressing NS gene were able to inhibit tumorigenesis induced by chemical carcinogens.However,the tissues not expressing NS gene were not able to inhibit tumorigenesis.Transgenic mice had no prohibition against the growth of exogenous tumor cells.NS gene plays a direct role in the antitumorigenesis and may be mainly selectively prohibit the malignant change of cells in which it expresses.