Effects of haemopoietic growth factors in combination with etoposide on sister chromatid exchange frequencies in peripheral blood mononuclear cells

Abstract

Prior to work on the influence of dosing and scheduling of the drug etoposide in bone marrow cells, the DNA-damaging effects of three haemopoietic growth factors, either alone or in combination with etoposide, were investigated. Sister chromatid exchange (SCE) frequencies in phytohaemagglutinin-stimulated mononuclear cells of six normal volunteers were used as an indicator of DNA damage. The effects of three growth factors on SCEs were investigated at concentrations ranging between 0 and 100 ng/ml and those of etoposide alone, at concentrations varying between 0 and 2 μM. The effect of combinations of growth factor (GF) and etoposide were assessed at a 40-ng/ml concentration of each cytokine and at 0.4 μM etoposide. Results showed not only a dose-dependent rise in SCE frequency in cells treated with etoposide but also a cytokine effect. Stem-cell factor did not cause a significant change in SCE numbers. However, cytokines with activity at the progenitor cell level induced small but significant increases in SCE numbers at concentrations of 50 and 100 ng/ml (P<0.001). Results of combination studies indicated a significant 60% increase in SCE numbers in cells treated with GF and etoposide as compared with etoposide alone (P<0.00001). This finding suggests a sensitivity of peripheral blood mononuclear cells to SCE induction by GFs given either as single agents or in combination with etoposide.