de Kok A J, Tates A D, Den Engelse L, Simons J W
Carcinogenesis. 1985 Nov;6(11):1565-70. doi: 10.1093/carcin/6.11.1565.
The role of chromosomal alterations, as opposed to gene mutations, in the origin of early stages of the in vitro transformation of Syrian hamster embryo (SHE) cells was investigated. For that purpose we compared the rates at which SHE cells recover from potential tumorigenic, mutagenic, clastogenic and cytotoxic damage if they are held in confluence in low serum medium for 3 or 6 days following a single treatment of N-ethyl-N-nitrosourea (ENU) before the cells are allowed to divide and to express this damage. The results show: (i) that frequencies of gene mutations remain constant; (ii) frequencies of sister chromatid exchange (SCE) and cytotoxicity decrease with very similar kinetics; and (iii) frequencies of chromatid aberrations and micronuclei decrease rapidly in the first 3 days, but slowly or not at all between days 3 and 6. Thus, all the mutational damage and a small fraction of the clastogenic damage still persist after 6 days confluent holding. From the two early stages of in vitro transformation studied, morphological transformation and enhanced fibrinolytic activity, the former shows similar kinetic behaviour as chromatid aberrations and micronuclei, whereas the kinetics of the latter correspond with those of gene mutations. Neither is correlated to SCE or cytotoxicity. Our results suggest that chromosomal alterations can play a major role in induction of morphological transformation of SHE cells. Insofar as enhanced fibrinolytic activity is due to a genetic change, gene mutations can be responsible. Our observations further indicate that different types of ENU-induced DNA lesions are involved in gene mutations, SCE and cytotoxicity, and clastogenic damage. We have reported the results of experiments analysing these relationships in another paper.
研究了染色体改变而非基因突变在叙利亚仓鼠胚胎（SHE）细胞体外转化早期阶段起源中的作用。为此，我们比较了SHE细胞在单次用N-乙基-N-亚硝基脲（ENU）处理后，若在低血清培养基中汇合培养3天或6天，然后再让细胞分裂并表达这种损伤，其从潜在致瘤、致突变、致染色体断裂和细胞毒性损伤中恢复的速率。结果表明：（i）基因突变频率保持恒定；（ii）姐妹染色单体交换（SCE）频率和细胞毒性以非常相似的动力学下降；（iii）染色单体畸变和微核频率在最初3天迅速下降，但在第3天至第6天之间下降缓慢或根本不下降。因此，在汇合培养6天后，所有的突变损伤和一小部分致染色体断裂损伤仍然存在。在所研究的体外转化的两个早期阶段，即形态转化和增强的纤溶活性中，前者表现出与染色单体畸变和微核相似的动力学行为，而后者的动力学与基因突变的动力学相对应。两者均与SCE或细胞毒性无关。我们的结果表明，染色体改变可能在SHE细胞形态转化的诱导中起主要作用。就增强的纤溶活性是由于基因变化而言，基因突变可能是原因。我们的观察进一步表明，不同类型的ENU诱导的DNA损伤参与了基因突变、SCE和细胞毒性以及致染色体断裂损伤。我们在另一篇论文中报告了分析这些关系的实验结果。
