Zajac-Kaye M, Ts'o P O
Cell. 1984 Dec;39(3 Pt 2):427-37. doi: 10.1016/0092-8674(84)90450-1.
We have used liposomes to deliver DNAase I inside normal Syrian hamster embryo (SHE) cells. We showed the entrance of DNAase I inside the cell by dose-dependent cytotoxicity; and the entrance of DNAase I into the nucleus by the induction of chromosomal aberrations and somatic mutation at the HPRT locus (but not at the Na+/K+ ATPase locus). The induction of neoplastic transformation in cultures treated by DNAase I-in-liposomes was manifested by increased saturation density, colony formation at low seeding density, colony formation in 1% serum and 0.3% agar, and tumorigenicity in 100% of injected animals. The acquisition of anchorage-independent growth became apparent only after 39-57 posttreatment population doublings. Thus damage to DNA alone can initiate the neoplastic transformation process; but for full expression of the neoplastic phenotypes, a long progression time is required for the acquisition of anchorage-independent growth and tumorigenicity.
我们已使用脂质体将脱氧核糖核酸酶I递送至正常叙利亚仓鼠胚胎(SHE)细胞内。我们通过剂量依赖性细胞毒性证明了脱氧核糖核酸酶I进入细胞内;并通过在次黄嘌呤磷酸核糖转移酶位点(而非钠钾ATP酶位点)诱导染色体畸变和体细胞突变,证明了脱氧核糖核酸酶I进入细胞核。脂质体包裹的脱氧核糖核酸酶I处理的培养物中肿瘤转化的诱导表现为饱和密度增加、低接种密度下的集落形成、1%血清和0.3%琼脂中的集落形成以及100%注射动物的致瘤性。只有在处理后39 - 57次群体倍增后,非锚定依赖性生长的获得才变得明显。因此,仅DNA损伤就能启动肿瘤转化过程;但对于肿瘤表型的完全表达,获得非锚定依赖性生长和致瘤性需要很长的进展时间。