Formation of cadaverine as an effect of alpha-difluoromethylornithine on chick embryo fibroblasts transformed by rous sarcoma virus.

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.