Vasudevan S, Qureshi I A, Mores L, Rao P M, Rajalakshmi S, Sarma D S
Department of Pathology, University of Toronto, Ontario, Canada.
Biochem Med Metab Biol. 1992 Jun;47(3):274-8. doi: 10.1016/0885-4505(92)90037-y.
Sparse fur hemizygous male mice are over 90% deficient in ornithine transcarbamylase and exhibit increased synthesis of orotic acid. Because our earlier studies have demonstrated that orotic acid is a liver tumor promoter in the rat, it was of interest to determine whether this genetic disorder also increases the risk of tumor promotion. The results revealed that the livers of mutant mice showed a fourfold increase in uridine nucleotides and a 50% decrease in adenosine nucleotides compared to corresponding controls, a pattern of nucleotide pool imbalance similar to that seen in the livers of rats exposed to orotic acid under promoting conditions. Creation of such an imbalance appears to be important for orotic acid to exert its promotional effects. Sparse fur mutant mouse may, therefore, be an ideal animal model to study the tumor-promoting effects of orotate.
毛发稀疏的半合子雄性小鼠鸟氨酸转氨甲酰酶缺乏超过90%，乳清酸合成增加。由于我们早期的研究表明乳清酸是大鼠肝脏肿瘤促进剂，因此确定这种遗传性疾病是否也会增加肿瘤促进风险很有意义。结果显示，与相应对照组相比，突变小鼠肝脏中的尿苷核苷酸增加了四倍，腺苷核苷酸减少了50%，这种核苷酸池失衡模式与在促进条件下接触乳清酸的大鼠肝脏中所见相似。产生这种失衡似乎对乳清酸发挥其促进作用很重要。因此，毛发稀疏的突变小鼠可能是研究乳清酸盐肿瘤促进作用的理想动物模型。
