Variability in sensitivity to arsenite does not correlate with arsenic accumulation rate in normal human lymphoblasts.
Variability in sensitivity to arsenite does not correlate with arsenic accumulation rate in normal human lymphoblasts.
复制标题
对亚砷酸盐敏感性的变化与正常人淋巴母细胞中砷的积累率无关。
DOI：
10.1023/b:mcbi.0000007263.27349.ae
复制
发表时间：
2004
影响因子：
4.3
通讯作者：
Rossman,TobyG
中科院分区：
文献类型：
--
作者：
Li,Ping;Uddin,AhmedN;Liu,Zijuan;Mukhopadhyay,Rita;Komissarova,ElenaV;Rosen,BarryP;Rossman,TobyG
砷是我们空气、水和食物中常见的环境污染物，但并不是每个饮用砷污染水的人都表现出中毒的临床症状。在不同供者的外周血淋巴细胞中，亚砷酸盐诱导的非整倍体、染色体畸变和姐妹染色单体交换也存在较大的个体间差异。淋巴母细胞是病毒永生化的淋巴细胞，保留了淋巴细胞的大部分特性。单个淋巴母细胞系在冷冻保存和随后的复苏后保留了它们的亚砷酸盐敏感性。我们测定了11个正常人淋巴母细胞系中73个[As]-亚砷酸盐的积累。最慢和最快的受试者之间的亚砷酸盐积累率变化为6.3倍。在14个淋巴母细胞系的测定显示变异亚砷酸盐的毒性作用，作为衡量的生长抑制。淋巴母细胞系的生长速度也各不相同，但生长速度和亚砷酸盐敏感性之间没有关系。令人惊讶的是，我们还发现砷的积累率和细胞的敏感性生长抑制之间没有相关性，这表明砷的积累率可能不是细胞对砷的敏感性的主要决定因素。使用RT-PCR，我们也无法检测到酵母亚砷酸盐外排基因ACR 3的人类同源物的证据。
Arsenic is a common environmental contaminant of our air, water and food, but not every individual who drinks arsenic-contaminated water shows clinical signs of toxicity. Large inter-individual variations are also found in arsenite-induced aneuploidy, chromosome aberrations and sister chromatid exchanges in peripheral blood lymphocytes from different human donors. Lymphoblasts are virally immortalized lymphocytes that retain most of the properties of lymphocytes. Individual lymphoblast cell lines retained their arsenite sensitivity after cryopreservation and subsequent revival. We measured the accumulation of73[As]-arsenite into lymphoblast lines derived from 11 normal individuals. Arsenite accumulation rate varied 6.3 fold between the slowest and the fastest subjects. Assays in 14 lymphoblast lines showed variability to the toxic effects of arsenite, as measured by growth inhibition. Lymphoblast lines also vary with regard to their growth rates, but there is no relationship between growth rate and arsenite sensitivity. Surprisingly, we also found no correlation between arsenite accumulation rate and cellular sensitivity to growth inhibition, suggesting that the arsenite accumulation rate may not be the main determinant of cellular sensitivity to arsenic. We were also unable to detect evidence for a human homolog for the yeast arsenite efflux gene ACR3, using RT-PCR.