Keshava N, Zhou G, Hubbs A F, Ensell M X, Ong T m
Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, m/s 3014, 1095 Willowdale Road, Morgantown, WV 26505-2845, USA.
Mutat Res. 2000 Mar 14;448(1):23-8. doi: 10.1016/s0027-5107(99)00226-2.
A large number of workers are potentially exposed to cadmium during mining and processing. Therefore, there is a concern regarding the potential carcinogenic hazards of cadmium to exposed workers. Studies have been performed to determine if cadmium chloride (CdCl(2)) can induce morphological cell transformation, DNA from CdCl(2)-induced transformed cells can transform other mammalian cells, and the transformed cells induced by CdCl(2) can form tumors in nude mice. BALB/c-3T3 cells were treated with different concentrations of CdCl(2) for 72 h. The frequency of transformed foci from each treatment was determined after cells were cultured for 4 to 5 weeks. DNAs from five CdCl(2)-induced transformed cell lines were isolated and gene transfection assay was performed using NIH-3T3 cells. Non-transformed BALB/c-3T3 cells and cells from 10 transformed cell lines induced by CdCl(2) were injected into both axillary regions of nude mice. Mice were screened once a week for the appearance and size of tumors. CdCl(2) caused a statistically significant, concentration-related increase in the transformation frequency. DNA from all five CdCl(2)-induced transformed cell lines tested was found to induce varying degrees of transfection-mediated transformation in NIH-3T3 cells. All 10 CdCl(2)-induced transformed cell lines formed fibrosarcomas in nude mice within 39 days of inoculation. Within this time period, no tumors were found in nude mice injected with non-transformed BALB/c-3T3 cells. These results indicate that CdCl(2) is capable of inducing morphological cell transformation and that the transformed cells induced by CdCl(2) are potentially tumorigenic.
大量工人在采矿和加工过程中可能接触镉。因此,人们担心镉对接触工人的潜在致癌危害。已经开展了多项研究,以确定氯化镉(CdCl₂)是否能诱导细胞形态转化、CdCl₂诱导的转化细胞的DNA能否转化其他哺乳动物细胞,以及CdCl₂诱导的转化细胞能否在裸鼠体内形成肿瘤。用不同浓度的CdCl₂处理BALB/c-3T3细胞72小时。细胞培养4至5周后,确定每种处理的转化灶频率。从五个CdCl₂诱导的转化细胞系中分离DNA,并使用NIH-3T3细胞进行基因转染试验。将未转化的BALB/c-3T3细胞和CdCl₂诱导的10个转化细胞系的细胞注射到裸鼠的双侧腋窝区域。每周对小鼠进行一次检查,观察肿瘤的出现和大小。CdCl₂导致转化频率出现统计学上显著的、与浓度相关的增加。在所测试的所有五个CdCl₂诱导的转化细胞系中,发现其DNA能在NIH-3T3细胞中诱导不同程度的转染介导的转化。所有10个CdCl₂诱导的转化细胞系在接种后39天内在裸鼠体内形成了纤维肉瘤。在此时间段内,注射未转化的BALB/c-3T3细胞的裸鼠未发现肿瘤。这些结果表明,CdCl₂能够诱导细胞形态转化,且CdCl₂诱导的转化细胞具有潜在的致瘤性。