多胺生物合成的抑制对转化细胞c－Ha－ras癌基因表达的调控

抗多胺代谢剂──二氟甲基鸟氨酸（ＤＦＭＯ）作用于经含点突变的Ｈａ－ｒａｓ基因片段转染的转化细胞（ＨＲ－１细胞）引起细胞生长的抑制，其抑制率随ＤＦＭＯ浓度的增加而增大，此时细胞多停滞于Ｇ_１期；多胺合成的关键酶鸟氨酸脱羧酶（ＯＤＣ）活性显著下降；Ｈａ－ｒａｓ癌基因ｍＲＮＡ及ｒａｓＰ~（２１）蛋白的表达受到抑制；而外源性腐胺与ＤＦＭＯ的同时加入可防止上述一系列改变的发生，说明ＤＦＭＯ使ＨＲ－１细胞某些表型向亲本细胞逆转的作用是与细胞多胺生物合成的抑制直接相关。

The Regulation of the Inhibition of Polyamine Biosynthesis to the Expression of c-Ha-ras Oncogene in Transformed Cells

The effects of the inhibitor of polyamine biosynthesis──DFMO on cell phenotype of HR-1 cells transformed by c-Ha-ras ￣(Val12) oncogene from parental cell line NIH 3T3 were studied.In the presence of DFMO in the culture medium,significant inhibition of cell growth of HR-1 occurred, and there was a dose-dependent effect. The analysis of phase distribution of cell cycle indicated that addition of DFMO resulted in the increase of G1-phase cells. The ODC activity of these cells was markedly decreased. The expressions of c-Ha-ras oncogene mRNA and P￣(21) protein were suppressed thoroughly. All of these changes resulted by DFMO could be prevented by the addition of exogenous putrescine.