Gallagher K E, Gray I
J Immunopharmacol. 1981;3(3-4):339-61. doi: 10.3109/08923978109031066.
Cadmium, as Cd2+, has become an environmental pollutant of significant proportions. We and others have reported that cadmium in in vitro culture can alter several metabolic parameters including the synthesis of RNA. In the present study, a detailed examination of the mechanism of inhibition was undertaken. Cadmium, at 30 microM, decreased cellular uptake of uridine as well as incorporation into RNA up to 60 microM. Above this concentration, uridine incorporation fell to zero while that associated with the lymphocytes remained at a significantly higher value. LPS caused an increase in the fraction of the precursor incorporated into RNA. In the presence of cadmium, the fraction incorporated by non-stimulated cells fell continually while in the stimulated cells, the fraction had increased at 10 microM above which it dropped until at the highest concentration it was as for the unstimulated lymphocytes. It was found that up to 30 microM the ability of LPS to stimulate the lymphocytes in the presence of cadmium was enhanced while above that concentration it decreased so that at 70 microM no stimulation occurred. Cadmium also inhibited the formation of phosphorylated intermediates from uridine with UTP the most affected and the unstimulated lymphocytes the more sensitive. From the study of the intermediate steps it was found that RNA synthesis was directly inhibited and the most sensitive of the several inhibitory points.
镉以Cd2+的形式已成为一种具有相当比例的环境污染物。我们和其他人曾报道，体外培养中的镉可改变包括RNA合成在内的若干代谢参数。在本研究中，对抑制机制进行了详细研究。30微摩尔的镉可降低细胞对尿苷的摄取以及高达60微摩尔时尿苷掺入RNA的量。高于此浓度时，尿苷掺入量降至零，而与淋巴细胞相关的量则保持在显著更高的值。脂多糖（LPS）导致掺入RNA的前体部分增加。在镉存在的情况下，未刺激细胞掺入的部分持续下降，而在刺激细胞中，该部分在10微摩尔时增加，高于此浓度则下降，直至在最高浓度时与未刺激淋巴细胞的情况相同。结果发现，在镉存在的情况下，高达30微摩尔时LPS刺激淋巴细胞的能力增强，而高于该浓度时则下降，以至于在70微摩尔时无刺激发生。镉还抑制了尿苷与三磷酸尿苷（UTP）形成磷酸化中间体，其中UTP受影响最大，未刺激的淋巴细胞更敏感。通过对中间步骤的研究发现，RNA合成受到直接抑制，且是几个抑制点中最敏感的。
