CHROMIUM DISTRIBUTION AND TOXICITY IN MAMMALIAN CELLS

我们将研究铬在细胞内的分布及其机制 哺乳动物细胞中铬毒性的研究。与铬(VI)，增加姐妹染色单体互换 频率出现在0.01微摩尔，而细胞的抑制 增殖发生在1.0微摩尔。铬(III)要少得多 有效。我们的工作假设是铬(VI)的遗传毒性效应 通常与抗增殖作用有关。 我们将研究51-铬(VI和III)在细胞内的运输和它们的 胞内细胞器的分布。我们预计铬的毒性 与染色质构象(DNA超结构)的变化有关。 我们的计划是：通过使用分析方法研究铬引起的细胞遗传学变化 其测量染色单体畸变率、染色体畸变率和姐妹染色单体互换率； 利用计算机辅助细胞大小调整设备检测细胞内的微小变化 细胞生长和细胞大小；发展耐铬和铬- 转化的细胞；使用各种分析来监控 这些细胞变种；研究铬对摄取 核苷酸前体和细胞核苷酸池；使用以下 生化研究的准备工作：完整细胞、通透性细胞、 研究铬对染色体的影响。 DNA合成的保真度以及染色质的构象 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.