Cell cycle phase specificity of action of methyl/glyoxal-bis (guanylhydrazone) and its relationship to polyamine biosynthesis on mouse leukaemia L1210 cells in culture

In an attempt to define more clearly a possible role for polyamine synthesis on the growth and cell cycle progression, the effects of methylglyoxal-bis (guanylhydrazone i.e. MGBG, an inhibitor of polyamine synthesis on the proliferation of mouse leukaemia L1210 cells in culture have been studied. Treatment of cells with MGBG resulted in a time and dosage dependent growth inhibition ultimately resulting in cytotoxicity. There was an early accumulation of G₁ cell population with a concomitant decrease in labelling index indicating a decrease in S phase cell population. Following prolonged treatment and at higher dose levels, an accumulation of cells also occurred in G₂ phase with a parallel decrease in mitotic index of cells, indicating a blockade in progression of cells from G₂ to M phase of cell cycle. A sudden early decrease (at 4 h, approximately 70 per cent of control) and a gradual decline later on (up to 15 per cent of control) in intracellular spermidine pools suggests a possible role of polyamines in cell cycle traverse. A possible explanation for these effects of MGBG has been offered.