title: Possible role of P-glycoprotein in cyclophosphamide resistance of transplanted mouse RLS lymphosarcoma.
abstract: The causes of different sensitivity of mouse LS lymphosarcoma and its resistant RLS variant to cyclophosphamide were studied. Division of LS and RLS cells stops in the G2/M phase 24 h after cyclophosphamide treatment, but this stop lasts for more than 48 h in LS cells and less than 24 h in RLS cells. DNA fragmentation, a marker of apoptosis, is observed only in LS cells starting from 24 h after cyclophosphamide treatment. LS and RLS strains do not differ by the expression of bcl-2, bcl-6, bax, bad, mdr1a, mdr1b genes and P-glycoprotein protein. The strains differ by transport activity of P-glycoprotein, tested by SYTO 16 substrate release from cells: activity of P-glycoprotein in RLS cells was 2-fold higher than in LS cells. Presumably, the resistance of RLS tumor to cyclophosphamide-induced apoptosis is a result of inhibition of the apoptotic cascade by P-glycoprotein which is functionally more active in these cells than in LS cells.
authors.affiliation: Institute of Molecular Biology and Biophysics, Siberian Division of Russian Academy of Sciences, Novosibirsk. agrish@soramn.ru
authors.forename: A Yu
authors.initials: AY
authors.lastname: Grishanova
authors.forename: E V
authors.initials: EV
authors.lastname: Melnikova
authors.forename: V I
authors.initials: VI
authors.lastname: Kaledin
authors.forename: V P
authors.initials: VP
authors.lastname: Nikolin
authors.forename: V V
authors.initials: VV
authors.lastname: Lyakhovich
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018906:Antineoplastic Agents, Alkylating; D011518:Proto-Oncogene Proteins; D003520:Cyclophosphamide