title: Purging of small cell lung cancer cells from human bone marrow using ethiofos (WR-2721) and light-activated merocyanine 540 phototreatment.
abstract: One limitation of autologous bone marrow transplantation for patients with cancer has been the presence of tumor cells in the bone marrow. Methods to eliminate tumor cells while preserving hematopoietic stem cells have been sought. The present study was performed to analyze the in vitro effectiveness of light-activated merocyanine 540 phototreatment (LAMP) and an aminothiol (ethiofos) as a marrow-purging regimen for small cell lung cancer (SCLC). Two human SCLC cell lines (ATCC HTB-119 and HTB-120) were treated with LAMP and exposed to light for varying periods of time up to 120 min. LAMP reduced SCLC cell proliferation and colony formation in a light exposure-dependent manner; colony formation was not totally inhibited until light exposure of 120 min was used. At this light exposure interval, multipotential hematopoietic progenitors, colony-forming units-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM), were substantially reduced. In an attempt to diminish hematopoietic toxicity, SCLC cells were incubated with ethiofos (formerly WR-2721) for 1 hour before LAMP. SCLC colony formation was eliminated at light exposure intervals (90 min or less) which had no inhibitory effect on CFU-GEMM. Ethiofos did not protect CFU-GEMM from LAMP inhibition at 120 min. Ethiofos alone had no effect on the SCLC or hematopoietic cells. When normal bone marrow was contaminated with 1 or 5% SCLC cells, ethiofos plus 60 min of LAMP eliminated SCLC cells but had no effect on CFU-GEMM. The results suggest that ethiofos sensitized SCLC cells to LAMP; thus ethiofos-enhanced LAMP may be an effective method for removing metastatic SCLC cells from bone marrow used for autologous marrow transplantation after high dose chemotherapy.
authors.affiliation: Department of Laboratory Hematology, Cleveland Clinic Foundation 44195-5139.
authors.forename: R C
authors.initials: RC
authors.lastname: Meagher
authors.forename: S A
authors.initials: SA
authors.lastname: Rothman
authors.forename: P
authors.initials: P
authors.lastname: Paul
authors.forename: P
authors.initials: P
authors.lastname: Koberna
authors.forename: C
authors.initials: C
authors.lastname: Willmer
authors.forename: P A
authors.initials: PA
authors.lastname: Baucco
mesh_terms: D004999:Amifostine / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D010778:Photochemotherapy; D011744:Pyrimidinones / Q000627:therapeutic use*; D011837:Radiation-Protective Agents; D014407:Tumor Cells, Cultured
chemical_list: D009946:Organothiophosphorus Compounds; D011744:Pyrimidinones; D011837:Radiation-Protective Agents; C003954:merocyanine dye; D004999:Amifostine