Fischbach M, Sabbioni E, Bromley P
Research Laboratories Dompè S.p.A. L'Aquila, Varese, Italy.
Cell Biol Toxicol. 1993 Apr-Jun;9(2):177-88. doi: 10.1007/BF00757579.
An in vitro test method for general metal toxicity screening was designed, based on the cellular response to stress. The expression of a transfected human growth hormone gene sequence driven by the human heat-shock protein 70 promoter in NIH/3T3 cells was used as marker of noxious contact with metal compounds. Out of a series of 31 metals, 17 were competent for inducing this stress response system. According to the effective concentration and to the intensity of the response, three different clusters of positive compounds emerged and were ranked as strong, intermediate strength and weak inducers. These results correlated well with data from other in vivo and in vitro metal toxicity studies, including LD50 in mice. Apparently the positive/negative compounds also fitted well with data from genotoxicity and carcinogenesis studies on metal salts.
基于细胞对应激的反应,设计了一种用于一般金属毒性筛选的体外测试方法。由人热休克蛋白70启动子驱动的转染人生长激素基因序列在NIH/3T3细胞中的表达被用作与金属化合物有害接触的标志物。在一系列31种金属中,有17种能够诱导这种应激反应系统。根据有效浓度和反应强度,出现了三种不同的阳性化合物簇,并被列为强、中等强度和弱诱导剂。这些结果与其他体内和体外金属毒性研究的数据(包括小鼠的半数致死剂量)相关性良好。显然,阳性/阴性化合物也与金属盐的遗传毒性和致癌性研究数据吻合良好。