Modification by caffeine of acute cytotoxic response of cultured L5178Y cells to hydroxyurea treatment

Abstract

The effect of caffeine (CAF) on acute cytotoxic response of L5178Y lymphoblasts to hydroxyurea (HU) treatment was studied. The following events were examined: abnormal cell enlargement (giant cell formation), the rate of recovery of cell reproduction and DNA synthesis after releasing the cells from the HU blockage, parental DNA breakage and cell death. The presence of CAF at nontoxic concentration prevented giant cell formation, enhanced cell growth inhibition and cell killing. The effect of CAF was variable, dependent on the duration of exposure to HU and the time of exposure to CAF. To obtain maximal effect, the continuous presence of CAF during HU treatment and posttreatment time was necessary. Hydroxyapatite chromatography assay of single strand (ss) and double strand (ds) fractions in parental DNA and the measurement of the rate of post-treatment recovery of DNA synthesis indicated that CAF enhanced HU-induced DNA lesions. It is concluded that the results give further evidence that even short HU treatment can damage not only newly formed but also parental DNA. The lesions are normally, at least partly repaired and can be expressed under the conditions of DNA repair inhibition.