Bachrach U, Shtorch A
Cancer Res. 1985 May;45(5):2159-64.
Chick embryo fibroblasts grew normally in the presence of 1 X 10(-3) to 10 X 10(-3) M alpha-difluoromethylornithine (DFMO). This drug did not interfere with protein and DNA synthesis of normal fibroblasts and of cells transformed by Rous sarcoma virus. The morphological appearance of normal and transformed cells was not altered by DFMO, as determined by scanning electron microscopy. Flow microfluorometric analyses also confirmed the notion that normal or transformed cells were not blocked by DFMO in the G1 phase of the cell cycle. As expected, DFMO reduced cellular putrescine levels. This diamine, however, was replaced by the analogue cadaverine (1,5-diaminopentane), which accumulated mainly in the transformed cells. The increase in cellular cadaverine levels was also demonstrated during the infection of chick embryo fibroblasts with a temperature-sensitive mutant of Rous sarcoma virus under permissive conditions. Under restrictive conditions (42 degrees C), less cadaverine accumulated in the infected cells. These findings suggest that diamines and polyamines are necessary for the transformation process and that blocking one pathway by DFMO leads to the activation of an alternative biosynthetic pathway.
鸡胚成纤维细胞在1×10⁻³至10×10⁻³M的α-二氟甲基鸟氨酸（DFMO）存在下正常生长。这种药物不干扰正常成纤维细胞和劳斯肉瘤病毒转化细胞的蛋白质和DNA合成。通过扫描电子显微镜测定，DFMO未改变正常细胞和转化细胞的形态外观。流式微荧光分析也证实了正常或转化细胞在细胞周期的G1期未被DFMO阻断这一观点。正如预期的那样，DFMO降低了细胞腐胺水平。然而，这种二胺被类似物尸胺（1,5-二氨基戊烷）取代，尸胺主要在转化细胞中积累。在允许条件下，用劳斯肉瘤病毒的温度敏感突变体感染鸡胚成纤维细胞期间，也证明了细胞尸胺水平的增加。在限制条件（42℃）下，感染细胞中积累的尸胺较少。这些发现表明二胺和多胺是转化过程所必需的，并且DFMO阻断一条途径会导致另一条生物合成途径的激活。
