Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000175351900037&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1791-7530
Externe Identifier
  • Clarivate Analytics Document Solution ID: 547UZ
  • PubMed Identifier: 12017294
ISSN
0250-7005
Ausgabe der Veröffentlichung
1A
Zeitschrift
ANTICANCER RESEARCH
Schlüsselwörter
  • apoptosis
  • drug resistance
  • PCR stop assay
Paginierung
231 - 234
Datum der Veröffentlichung
2002
Status
Published
Titel
Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells
Sub types
  • Article
Ausgabe der Zeitschrift
22

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
In addition to signaling proliferation, growth factors may contribute to the persistence of hematopoietic tumors upon chemotherapeutical challenge. In multiple myeloma, malignant growth is mediated either by paracrine interleukin-6 (IL-6) elaborated by bone marrow stromal cells or via autocrine loops by malignant myeloma cells themselves. Although melphalan is one of the most active drugs in this tumor entity, the development of drug resistance frequently impedes cure of patients by attenuating melphalan-induced DNA-damage. We analyzed whether IL-6 protects XG-1 cells and plasma cells of a patient suffering from end-stage multiple myeloma (plasma cell leukemia) from melphalan with respect to DNA damage and DNA repair. Investigating the housekeeping gene glucose-6-phosphate dehydrogenase (G6PD) by using a PCR-stop assay, we found that there was more DNA damage in the G6PD gene of IL-6 deprived XG-1 and the patient's plasma cells, respectively, than in those with IL-6 supplementation. After cessation of melphalan exposure and 24 hours post-incubation in melphalan-free medium, DNA repair was observed in the patient's plasma cells but not in XG-1 cells. There was more DNA repair with IL-6 addition than without IL-6 addition. Similarly, the apoptotic cell fractions, as measured by flow cytometry, were lower if IL-6 was added to the medium. These results indicate that IL-6 may contribute to drug resistance in multiple myeloma.
Addresses
  • Medizinische Klinik IV, RWTH Aachen, Germany. efferth@vcrp.de
Autoren
eISSN
1791-7530
Externe Identifier
  • PubMed Identifier: 12017294
Open access
false
ISSN
0250-7005
Ausgabe der Veröffentlichung
1A
Zeitschrift
Anticancer research
Schlüsselwörter
  • Plasma Cells
  • Humans
  • Multiple Myeloma
  • DNA Damage
  • Melphalan
  • Glucosephosphate Dehydrogenase
  • Antineoplastic Agents, Alkylating
  • Interleukin-6
  • Flow Cytometry
  • Polymerase Chain Reaction
  • Apoptosis
  • DNA Repair
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Aged
  • Female
Sprache
eng
Medium
Print
Paginierung
231 - 234
Datum der Veröffentlichung
2002
Status
Published
Datum der Datenerfassung
2002
Titel
Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
22

Data source: Europe PubMed Central

Abstract
In addition to signaling proliferation, growth factors may contribute to the persistence of hematopoietic tumors upon chemotherapeutical challenge. In multiple myeloma, malignant growth is mediated either by paracrine interleukin-6 (IL-6) elaborated by bone marrow stromal cells or via autocrine loops by malignant myeloma cells themselves. Although melphalan is one of the most active drugs in this tumor entity, the development of drug resistance frequently impedes cure of patients by attenuating melphalan-induced DNA-damage. We analyzed whether IL-6 protects XG-1 cells and plasma cells of a patient suffering from end-stage multiple myeloma (plasma cell leukemia) from melphalan with respect to DNA damage and DNA repair. Investigating the housekeeping gene glucose-6-phosphate dehydrogenase (G6PD) by using a PCR-stop assay, we found that there was more DNA damage in the G6PD gene of IL-6 deprived XG-1 and the patient's plasma cells, respectively, than in those with IL-6 supplementation. After cessation of melphalan exposure and 24 hours post-incubation in melphalan-free medium, DNA repair was observed in the patient's plasma cells but not in XG-1 cells. There was more DNA repair with IL-6 addition than without IL-6 addition. Similarly, the apoptotic cell fractions, as measured by flow cytometry, were lower if IL-6 was added to the medium. These results indicate that IL-6 may contribute to drug resistance in multiple myeloma.
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/12017294
ISSN
0250-7005
Ausgabe der Veröffentlichung
1A
Zeitschrift
Anticancer Res
Schlüsselwörter
  • Aged
  • Antineoplastic Agents, Alkylating
  • Apoptosis
  • DNA Damage
  • DNA Repair
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Flow Cytometry
  • Glucosephosphate Dehydrogenase
  • Humans
  • Interleukin-6
  • Melphalan
  • Multiple Myeloma
  • Plasma Cells
  • Polymerase Chain Reaction
Sprache
eng
Country
Greece
Paginierung
231 - 234
Datum der Veröffentlichung
2002
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2002
Titel
Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
22

Data source: PubMed

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