CHROMIUM DISTRIBUTION AND TOXICITY IN MAMMALIAN CELLS

我们将研究铬在细胞内的分布及其机制 铬对哺乳动物细胞的毒性。 Cr（VI）增加SCE 频率发生在0.01微摩尔，而细胞的抑制 增殖发生在1.0微摩尔。 Cr（III）含量少得多 有效 我们的工作假设是，Cr（VI）的遗传毒性作用 通常与抗增殖作用有关。 我们将研究51-Cr（VI和III）进入细胞的转运及其在细胞中的作用。 分布于细胞内细胞器。 我们认为铬的毒性 与染色质构象（DNA超结构）的变化有关。 我们的计划是：通过检测来研究铬引起的细胞遗传学变化 其测量染色单体畸变、染色体畸变和SCE; 利用计算机辅助细胞大小测定设备检测细胞中的微小变化， 细胞生长和细胞大小;开发铬抗性和铬- 转化的细胞;使用各种分析来监测 这些细胞变体;研究铬对摄取的影响， 核苷酸前体和细胞核苷酸库;使用以下 用于生物化学研究的制剂：完整细胞，透化细胞， 类核和分离的染色体;研究铬的影响， DNA合成的保真度，并在这些染色质的构象 准备工作

We will study the intracellular distribution of chromium and the mechanisms of chromium toxicity in mammalian cells. With Cr(VI), increased SCE frequency occurred at 0.01 micromolar, whereas the inhibition of cell proliferation occurred at 1.0 micromolar. Cr(III) was much less effective. Our working hypothesis is that the genotoxic effects of Cr(VI) are causually related to the antiproliferative effects. We will study the transport of 51-Cr (VI and III) into cells and of their distribution in intracellular organelles. We expect that chromium toxicity is associated with changes in chromatin conformation (DNA superstructure). Our plan is to: study cytogenetic changes by chromium by using assays which measure chromatid aberrations, chromosomal aberrations and SCE; utilize computer-aided cell sizing equipment to detect small changes in cell growth and cell size; develop chromium- resistent and chromium - transformed cells; use a variety of analyses to monitor alterations in these cell variants; study the effects of chromium on the uptake of nucleotide precursors and cellular nucleotide pools; use the following preparations for biochemical studies: intact cells, permeabilized cells, nucleoids and isolated chromosomes; study the effects of chromium on the fidelity of DNA synthesis, and on the conformation of chromatin in these preparations.