Cell cycle kinetics of Chinese hamster (CHO) cells treated with the iron-chelating agent picolinic acid

Spontaneously transformed (tumorigenic) Chinese hamster cells (line CHO) do not exhibit picolinic acid-sensitive G1 and G2 cell cycle arrest points observed in normal and virus-transformed cells. Rather, picolinic acid arrests CHO cells in S phase only and produces culture growth behaviour similar to that produced by hydroxyurea. Prolonged treatment with picolinic acid permits a slow but significant traverse of cells through S phase. Thus, like hydroxyurea, picolinic acid is not a useful agent for synchronizing exponential CHO cells, but it can be used to resynchronize cultures in early S phase if a previous synchronization procedure (such as isoleucine deprivation) is used. The iron chelating properties of picolinic acid, and the similarities of its effects on cultured cells to those of hydroxyurea and the iron-chelating drug desferrioxamine, suggest that picolinic acid inhibits DNA synthesis by interfering with the iron-dependent production of a stable free organic radical which is essential for the ribonucleotide reductase formation of deoxyribonucleotides.