摘要
给予３７．５，７５和１５０ｍｇ·Ｌ－１环磷酰胺（ＣＰ）均可稳定地引起叙利亚地鼠胚胎细胞的表型转化．转化细胞在传至９９代时，仍然具有旺盛的分裂增殖能力，对细胞生长因子的依赖程度下降，转化细胞可因植物凝集素的存在而发生凝集，具有在软琼脂培养基上形成集落的能力，表现出抛锚独立性生长特性；接种同种动物及无胸腺裸鼠后能形成肿瘤．瘤切片病理观察显示所形成肿瘤均为分化程度较高的纤维肉瘤，从而证明ＣＰ能够诱导叙利亚地鼠胚胎细胞发生恶性转化．
In previous study, the malignant transformation of Syrian hamster embryo(SHE) cell induced by cyclophosphamde(CP), following the formation of fibroblast sarcoma, had been identified. In this study, the molecular characters of the transformation were investigated by molecular hybridization, DNA sequencing and RTPCR. The study indicated that not only cmyc oncogene was activated by amplification, but also both Haras and Kiras oncogene had been mutated.The mutation of Haras oncogene fragment(207 bp) had been identified. The results showed that a 35 base substitution occurred. Most of the substitution appeared in the 3rd position of codon, only 2 in the 1st position. But only the GT transvertion of 3 rd base of codon 67 caused methionine to be substituted by isoleucine. Other base replacement did not alter the coded amino acid. The results also showed that there was no site specificity in Haras mutation. The mutation of p53 tumor suppressor gene had also been identified. The results show that the mutation may belong to point mutation. Therefore, the activation of cmyc, Haras, Kiras oncogene and inactivation or other changes of p53 tumor suppressor gene by mutation, along with their cooperation, may be the molecular mechanism of the malignant transformation of SHE cell induced by CP.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
1998年第3期192-195,共4页
Chinese Journal of Pharmacology and Toxicology
关键词
环磷酰胺
胚胎细胞
恶性转化
地鼠
cyclophosphamide
Syrian hamster embryo
oncogenes
genes, suppressor, tumor
mutation
gene amplification
