Oshimura M, Hesterberg T W, Tsutsui T, Barrett J C
Cancer Res. 1984 Nov;44(11):5017-22.
The cytogenetic effects of chrysotile asbestos on Syrian hamster embryo cells in vitro were investigated at doses which induced morphological and neoplastic transformation but which failed to induce measurable gene mutations in the cells at two genetic loci. Chrysotile asbestos treatment of the cells significantly induced chromosome changes in a dose-dependent manner. Up to 50% of the cells had chromosome abnormalities in number or structure following treatment with asbestos (2.0 micrograms/sq cm) for 48 hr. Numerical chromosome changes were the most pronounced abnormalities although significant increases in metaphases with other chromosome aberrations (breaks, fragments, exchanges, and/or dicentrics) and cells with binuclei or micronuclei were also observed. A linear relationship was observed between the incidences of cells with tetraploid metaphases and binucleated cells, suggesting that binucleation and tetraploidy are related. Cytogenetic effects of other mineral dusts were also tested 48 hr following treatment at a concentration of 2.0 micrograms/sq cm. Crocidolite asbestos was less potent than chrysotile asbestos in its ability to induce cell transformation and cytogenetic damage. Treatment of the cells with thin glass fibers (Code 100) was also able to induce cell transformation and cytogenetic effects, but thick glass fibers (Code 110) were much less potent for both endpoints. Milling of the thin glass fibers decreased the length of the fibers and abolished their ability to induce cell transformation and cytogenetic effects. Nonfibrous alpha-quartz induced neither cell transformation nor cytogenetic effects at the dose of 2.0 micrograms/sq cm. The results indicate that the physical characteristics of the fibers determine their ability to induce cell transformation and their ability to induce chromosome mutations, suggesting a possible mechanistic relationship.
研究了温石棉在体外对叙利亚仓鼠胚胎细胞的细胞遗传学效应,所用剂量能诱导形态学和肿瘤性转化,但未能在两个基因位点诱导细胞中可检测到的基因突变。用温石棉处理细胞以剂量依赖性方式显著诱导染色体变化。用石棉(2.0微克/平方厘米)处理48小时后,高达50%的细胞出现数量或结构上的染色体异常。尽管也观察到具有其他染色体畸变(断裂、片段、交换和/或双着丝粒)的中期细胞以及具有双核或微核的细胞显著增加,但染色体数量变化是最明显的异常。观察到具有四倍体中期的细胞和双核细胞的发生率之间呈线性关系,表明双核化和四倍体化有关。在以2.0微克/平方厘米的浓度处理48小时后,还测试了其他矿物粉尘的细胞遗传学效应。青石棉在诱导细胞转化和细胞遗传学损伤方面的能力不如温石棉。用细玻璃纤维(代码100)处理细胞也能够诱导细胞转化和细胞遗传学效应,但粗玻璃纤维(代码110)在这两个终点方面的效力要低得多。细玻璃纤维的研磨缩短了纤维长度,并消除了它们诱导细胞转化和细胞遗传学效应的能力。在2.0微克/平方厘米的剂量下,非纤维性α-石英既不诱导细胞转化也不诱导细胞遗传学效应。结果表明,纤维的物理特性决定了它们诱导细胞转化的能力以及诱导染色体突变的能力,提示可能存在机制上的关系。