Bacsi Attila, Aguilera-Aguirre Leopoldo, German Peter, Kruzel Marian L, Boldogh Istvan
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
J Exp Ther Oncol. 2006;5(4):249-59.
Colostrinin (CLN), a uniform mixture of low-molecular weight, proline-rich polypeptides, induces neurite outgrowth of pheochromocytoma cells, extends the lifespan of diploid fibroblast cells, inhibits beta amyloid-induced apoptosis and resulted in improved cognitive function when administered to Alzheimer's patients. Here we investigated CLN's antimutagenic activity in cells stressed oxidatively or exposed to chemical or physical agents. Our data show that CLN did not alter cell cycle kinetics and cloning efficiency, while it inhibited the development of spontaneous mutations at the coding region of the hypoxanthine phosphoribosyl-transferase (hprt) gene in Chinese hamster V79 cells. In a dose-dependent manner, CLN lowered reactive oxygen species (ROS)-induced frequency of cells resistant to 6-thioguanine (6-TG) to nearly background level. Likewise, CLN decreased the frequency of methyl methanesulfonate- or mitomycin C-induced mutations in V79 cells. Notably, CLN (at 100, 250, and 500 ng per ml concentrations) decreased UVA-induced mutation frequency, while only the highest dose of CLN also decreased significantly the number of UVB-induced 6-TG-resistant mutant cells. Similar results were obtained using cell cultures of human origin. Overall, our data show that CLN significantly lowers the mutation frequency that develops spontaneously or is induced by ROS, chemical and physical agents. CLN itself has no mutagenic activity. Therefore, CLN may be used in human therapies systemically and/or locally for the prevention of diseases associated with sequence alterations in genomic and mitochondrial DNA.
初乳素（CLN）是一种低分子量、富含脯氨酸的多肽的均匀混合物，可诱导嗜铬细胞瘤细胞的神经突生长，延长二倍体成纤维细胞的寿命，抑制β淀粉样蛋白诱导的细胞凋亡，并在给予阿尔茨海默病患者时改善认知功能。在此，我们研究了CLN在氧化应激细胞或暴露于化学或物理因子的细胞中的抗诱变活性。我们的数据表明，CLN不会改变细胞周期动力学和克隆效率，同时它抑制了中国仓鼠V79细胞次黄嘌呤磷酸核糖转移酶（hprt）基因编码区自发突变的发生。CLN以剂量依赖的方式将活性氧（ROS）诱导的对6-硫鸟嘌呤（6-TG）耐药的细胞频率降低至接近背景水平。同样，CLN降低了甲磺酸甲酯或丝裂霉素C诱导的V79细胞中的突变频率。值得注意的是，CLN（浓度为每毫升100、250和500纳克）降低了紫外线A诱导的突变频率，而只有最高剂量的CLN也显著降低了紫外线B诱导的对6-TG耐药的突变细胞数量。使用人类来源的细胞培养物也获得了类似的结果。总体而言，我们的数据表明，CLN显著降低了自发产生或由ROS、化学和物理因子诱导产生的突变频率。CLN本身没有诱变活性。因此，CLN可全身和/或局部用于人类治疗，以预防与基因组和线粒体DNA序列改变相关的疾病。
