Kravchenko I V, Furalyov V A, Vasylieva L A, Pylev L N
Laboratory of Natural Carcinogens, Cancer Research Center, Russian Academy of Medical Sciences, Moscow.
Teratog Carcinog Mutagen. 1998;18(3):141-51.
The processes of spontaneous and asbestos-induced transformation of rat mesothelium were studied using cell cultures obtained in the laboratory. The same changes in cell properties were established in both spontaneous and asbestos-induced transformation: change in epidermal growth factor (EGF) response, in some cases appearance of fibroblast-like cells instead of polygonal ones, appearance of multilayer cell growth foci, and ability to grow in semisolid agar. The response to fibroblast growth factor, insulin-like growth factor 1, and insulin did not change during transformation as well as the P450 system activity measured by benz(a)pyrene (BP) and 7,12-dimethylbenzanthracene (DMBA) cytotoxicity. The asbestos-induced transformation began earlier than the spontaneous one. EGF began to stimulate mesothelium proliferation instead of its inhibition at 6-7 passages in the case of asbestos-induced transformation, whereas during spontaneous transformation this change began at 9-10 passages. Elongated rather than polygonal cells appeared at 10-11 instead of 17-18 passages (this morphological change did not take place at all lines studied). The ability to grow in semisolid agar was found at 14-16 passages with asbestos and at 22-24 passages without it. The results allow us to propose the necessity of a positive EGF response for mesothelial cell transformation and the similarity of mechanisms of spontaneous and asbestos-induced transformation.
利用实验室获得的细胞培养物,对大鼠间皮的自发转化过程和石棉诱导的转化过程进行了研究。在自发转化和石棉诱导的转化中均发现细胞特性发生了相同的变化:表皮生长因子(EGF)反应改变,在某些情况下出现成纤维细胞样细胞而非多边形细胞,出现多层细胞生长灶,以及在半固体琼脂中生长的能力。在转化过程中,对成纤维细胞生长因子、胰岛素样生长因子1和胰岛素的反应以及通过苯并(a)芘(BP)和7,12-二甲基苯并蒽(DMBA)细胞毒性测定的P450系统活性均未改变。石棉诱导的转化比自发转化开始得更早。在石棉诱导的转化中,EGF在第6 - 7代开始刺激间皮细胞增殖而非抑制,而在自发转化中,这种变化在第9 - 10代开始。在第10 - 11代而非第17 - 18代出现了伸长的而非多边形的细胞(并非在所有研究的细胞系中都发生这种形态变化)。在有石棉存在的情况下,在第14 - 16代发现了在半固体琼脂中生长的能力,而在无石棉的情况下则在第22 - 24代发现。这些结果使我们提出,EGF阳性反应对于间皮细胞转化是必要的,并且自发转化和石棉诱导的转化机制具有相似性。