Rider S H, Mazzullo H A, Davis M B, Delhanty J D
J Med Genet. 1986 Apr;23(2):131-44. doi: 10.1136/jmg.23.2.131.
Growth in low serum and cell saturation density was investigated in 20 skin fibroblast cultures from 17 patients with the autosomal dominant cancer prone condition, familial polyposis coli (FPC). Compared with non-fetal control cultures, the grouped FPC cultures showed significantly better growth in low serum and approximately 30% increase in saturation density. Neither of these properties was correlated with high tetraploidy or clonal rearrangement of the chromosomes. No difference in response to epidermal growth factor was demonstrable between cultures from normal and affected subjects. The tumour promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), had no differential effect on growth in high and low density cultures of FPC and normal cells in short term experiments; both cell types displayed a biphasic response to the agent at low cell density. However, in long term experiments FPC skin cultures showed growth stimulation and greater resistance to the toxic effects of TPA than normal cells. Cells from both fetal and non-fetal controls as well as from FPC subjects displayed anchorage independent growth after treatment with TPA, but in general FPC cultures from skin and colon responded to a greater extent than non-fetal controls. Marked change in tetraploidy after treatment was evident only in those FPC and control cultures which were highly chromosomally abnormal. Both groups showed a slight increase in stable and unstable chromosome rearrangements with treatment but one FPC culture became totally chromosomally abnormal and cloned in agar with high efficiency, as did one of the treated fetal controls which, however, had normal chromosomes.
对17例患有常染色体显性遗传性癌症易感疾病——家族性结肠息肉病(FPC)患者的20份皮肤成纤维细胞培养物进行了低血清生长和细胞饱和密度研究。与非胎儿对照培养物相比,FPC培养物组在低血清中生长明显更好,饱和密度增加约30%。这些特性均与高四倍体或染色体克隆重排无关。正常受试者和患病受试者的培养物对表皮生长因子的反应没有差异。在短期实验中,肿瘤启动子十四烷酰佛波醇乙酯(TPA)对FPC和正常细胞的高密度和低密度培养物的生长没有差异影响;在低细胞密度下,两种细胞类型对该试剂均表现出双相反应。然而,在长期实验中,FPC皮肤培养物显示出生长刺激,并且比正常细胞对TPA的毒性作用具有更大的抗性。胎儿和非胎儿对照以及FPC受试者的细胞在用TPA处理后均表现出不依赖贴壁生长,但一般来说,皮肤和结肠的FPC培养物比非胎儿对照反应程度更大。仅在那些染色体高度异常的FPC和对照培养物中,处理后四倍体有明显变化。两组在处理后稳定和不稳定染色体重排均略有增加,但一份FPC培养物完全染色体异常并在琼脂中高效克隆,处理后的一份胎儿对照也是如此,不过其染色体正常。