Differential effects of inhibition of polyamine biosynthesis on cell cycle traverse and structure of the prematurely condensed chromosomes of normal and transformed cells

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Abstract
The points in the cell cycle at which normal and transformed cells become arrested as a result of polyamine deprivation were determined. Treatment of normal (human fibroblast line PA2 and mouse 3T3) and transformed (CHO, HeLa and SV3T3) cells with methylglyoxal bis(guanyl-hydrazone) resulted in a significant decrease in the levels of spermidine and spermine, which was associated with an inhibition of growth. Examination of the prematurely condensed chromosomes (PCC) of the polyamine-depleted cells revealed that normal fibroblasts were preferentially arrested in early G1 phase while a majority of cells in the transformed lines were blocked in S phase. A close examination of the PCC of the transformed cells indicated a significant decrease in the number of DNA replication sites. Polyamines apparently have an important role in DNA chain initiation.