Cell cycle related uptake, retention and toxicity of idarubicin, daunorubicin and doxorubicin.

Exponentially growing Molt-4 cells were separated by means of counterflow centrifugation into fractions enriched for cells in early G1, late G1, S, or G2+M phase of the cell cycle. Subsequently, cells were exposed for 2 h to Idarubicin (Ida, 0.02-0.15 microgram/ml). Daunorubicin (Dnr, 0.1-0.75 microgram/ml) or Doxorubicin (Dox, 0.1-0.75 microgram/ml). Drug uptake, measured by flow cytometry, increased progressively with cell cycle traverse from early G1-to M-phase. The relative fraction of drug lost following an extensive wash procedure was 72% in case of Ida and 23% for Dnr and Dox and was independent of the cell cycle phase. Inhibition of DNA synthesis was determined by qualitative flow cytometric analysis of 5-iodo-2'-deoxyuridine (IdUrd) incorporation into DNA. The three drugs showed a similar gradual increase of inhibition of DNA synthesis from G1 to G2+M phase, demonstrating that cell cycle phase dependency of drug toxicity applies to all three anthracyclines studied.