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采用杂交，测序，ＲＴ－ＰＣＲ等方法对环磷酰胺（ＣＰ）转化的不同叙利亚地鼠胚胎（ＳＨＥ）细胞株癌基因和抑癌基因进行了分析，结果表明，ｃ－ｍｙｃ癌基因以扩增的方式被激活，在Ｈａ－ｒａｓ和Ｋｉ－ｒａｓ癌基因上均存在着突变．在对Ｈａ－ｒａｓ２０７ｂｐ的一段ｃＤＮＡ序列分析中发现，总共发生了３５处碱基对的替换，除两处是在密码子的第一位碱基外，其余均发生于第三位碱基上，但除第６７位密码子的第三位碱基由于Ｇ－Ｔ颠换导致所编码的甲硫氨酸被异亮氨酸取代外，其余碱基的替换均未导致氨基酸的改变．分析还表明，ＣＰ致Ｈａ－ｒａｓ癌基因的突变无位点专一性．结果还表明，ｐ５３抑癌基因也发生了突变，并且可能属于点突变性质．因此，ＣＰ引起的ＳＨＥ细胞恶性转化的分子机理可能是以点突变和基因扩增的方式引起ｃ－ｍｙｃ，Ｋｉ－ｒａｓ，Ｈａ－ｒａｓ癌基因的激活及ｐ５３抑癌基因的失活或表达改变
Cytogenes and tumor suppressor genes of Syrian hamster embryo (SHE) cell lines transformed with cyclophosphamide (CP) were analyzed by hybridization, sequencing, RT-PCR and other methods. The results showed that the c-myc oncogene was amplified by amplification Is activated, there are mutations in Ha-ras and Ki-ras oncogene. A partial cDNA sequence analysis of Ha-ras207bp revealed that a total of 35 base-pair substitutions occurred, except for the first two bases of the codon and the third base. Except that the third base of codon 67 replaced the isoleucine encoded by methionine due to G-T transversion, and the other base substitutions did not lead to amino acid changes. Analysis also showed that CP-induced Ha-ras oncogene mutation without site specificity. The results also show that p53 tumor suppressor gene mutations have occurred, and may belong to point mutation properties. Therefore, the molecular mechanism of CP-induced malignant transformation of SHE cells may induce the activation of c-myc, Ki-ras and Ha-ras oncogenes and the inactivation or expression change of p53 tumor suppressor gene by point mutation and gene amplification