EFFECTS OF HEMATOPOIETIC GROWTH-FACTORS IN COMBINATION WITH ETOPOSIDEON SISTER-CHROMATID EXCHANGE FREQUENCIES IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Prior to work on the influence of dosing and scheduling of the drug et oposide in bone marrow cells, the DNA-damaging effects of three haemop oietic growth factors, either alone or in combination with etoposide, were investigated. Sister chromatid exchange (SCE) frequencies in phyt ohaemagglutinin-stimulated mononuclear cells of six normal volunteers were used as an indicator of DNA damage. The effects of three growth f actors on SCEs were investigated at concentrations ranging between 0 a nd 100 ng/ml and those of etoposide alone, at concentrations varying b etween 0 and 2 mu M. The effect of combinations of growth factor (GF) and etoposide were assessed at a 40-ng/ml concentration of each cytoki ne and at 0.4 mu M etoposide. Results showed not only a dose-dependent rise in SCE frequency in cells treated with etoposide but also a cyto kine effect. Stem-cell factor did not cause a significant change in SC E numbers. However, cytokines with activity at the progenitor cell lev el induced small but significant increases in SCE numbers at concentra tions of 50 and 100 ng/ml (P < 0.001). Results of combination studies indicated a significant 60% increase in SCE numbers in cells treated w ith GF and etoposide as compared with etoposide alone (P < 0.00001). T his finding suggests a sensitivity of peripheral blood mononuclear cel ls to SCE induction by GFs given either as single agents or in combina tion with etoposide.