title: 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 microM. 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 microM 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.
authors.affiliation: Barry Reed Oncology Laboratory, St. Bartholomew's Hospital, West Smithfield, London, UK.
authors.forename: W M
authors.initials: WM
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Bamford
authors.forename: M
authors.initials: M
authors.lastname: Slevin
authors.forename: S P
authors.initials: SP
authors.lastname: Joel
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004249:DNA Damage / Q000187:drug effects*; D004347:Drug Interactions; D005047:Etoposide / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor