Sanford K K, Parshad R, Stanbridge E J, Frost J K, Jones G M, Wilkinson J E, Tarone R E
Cancer Res. 1986 Apr;46(4 Pt 2):2045-9.
The relationship between tumorigenicity and enhanced chromosomal radiosensitivity during the G2 cell cycle phase was examined through the use of nontumorigenic human cell hybrids and their nontumorigenic and tumorigenic segregants. The hybrid cells were produced by fusion of a normal and tumor cell. The parental lines, including HeLa and three fibroblast lines, one of skin and two of fetal lung origin, were also examined. The tumorigenic lines, which had cytological features associated with clinical cancer, showed a significantly higher incidence of chromatid breaks and gaps following X-irradiation during G2 than the normal skin line or the nontumorigenic hybrids. The hybrids and their nontumorigenic subclones had cytological features which are predominantly found with a benign clinical course and had the G2 chromosomal radiosensitivity more characteristic of the normal parental cells. Like tumorigenic cells, fetal cells exhibited enhanced G2 chromosomal radiosensitivity which could be suppressed in fetal X tumor cell hybrids. This observation suggests that the molecular basis for radiosensitivity in fetal cells differs from that of tumor cells. The enhanced G2 chromosomal radiosensitivity of a tumor cell, which appears to result from deficient DNA repair, is suppressed by fusion with a normal cell. Thus, the radiosensitivity, like tumorigenicity, behaves as a recessive trait. Although a Mendelian analysis is not possible with this material, the segregation of enhanced G2 chromosomal radiosensitivity with the neoplastic phenotype suggests that the two may be genetically linked.
通过使用非致瘤性人类细胞杂种及其非致瘤性和致瘤性分离株，研究了G2细胞周期阶段致瘤性与染色体辐射敏感性增强之间的关系。杂种细胞是由正常细胞和肿瘤细胞融合产生的。还检查了包括HeLa和三种成纤维细胞系（一种来自皮肤，两种来自胎儿肺）在内的亲代细胞系。具有与临床癌症相关细胞学特征的致瘤性细胞系，在G2期X射线照射后，染色单体断裂和裂隙的发生率明显高于正常皮肤细胞系或非致瘤性杂种细胞。杂种细胞及其非致瘤性子克隆具有主要见于良性临床病程的细胞学特征，并且其G2染色体辐射敏感性更具有正常亲代细胞的特征。与致瘤性细胞一样，胎儿细胞表现出增强的G2染色体辐射敏感性，这在胎儿X肿瘤细胞杂种中可被抑制。这一观察结果表明，胎儿细胞辐射敏感性的分子基础与肿瘤细胞不同。肿瘤细胞增强的G2染色体辐射敏感性似乎是由DNA修复缺陷导致的，与正常细胞融合后这种敏感性会被抑制。因此，辐射敏感性与致瘤性一样，表现为隐性性状。尽管用这种材料无法进行孟德尔分析，但G2染色体辐射敏感性增强与肿瘤表型的分离表明两者可能存在遗传联系。
