title: Lithium and hydrocortisone interactions on cell growth and gene expression in human promyelocytic leukemia (HL60).
abstract: Lithium (Li) and hydrocortisone (HC) modify gene expression as well as stimulate human hematopoiesis in vivo and in vitro. The responses of blood-forming tissues, to these natural substances individually, are closely similar. However, clonogenic co-culture experiments, using normal human bone marrow cells, have revealed that the effects of Li and HC are not additive but rather mutually inhibitory. Studies of HL-60 cells in suspension indicate that growth of this human promyelocytic leukemic line is enhanced by HC at 10(-6) M, a "therapeutic" plasma concentration. This phenomenon is abrogated by the co-addition of Li at 3 x 10(-4) M, likewise a "therapeutic" plasma concentration. Neither substrate exerts any influence on the morphological or cytochemical features of differentiation which accompany exposure of HL-60 cells to dimethyl sulphoxide (DMSO), retinoic acid (RA), tetradecanoyl phorbol acetate (TPA) or sodium butyrate. In contrast, the expression of c-fms, a cellular proto-oncogene which codes for the CSF-1 (monocyte-macrophage colony-stimulating factor) surface membrane receptor, is modified by Li in the presence of the differentiation induction agents DMSO and RA which promote the development of mature granulocytes from HL-60 cells. These observations afford further insights into the humoral mechanisms which modulate the expression of genes involved in the regulation of hematopoiesis.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: S C
authors.initials: SC
authors.lastname: Knight
authors.forename: D
authors.initials: D
authors.lastname: Harnish
authors.forename: E
authors.initials: E
authors.lastname: Scheid
authors.forename: M
authors.initials: M
authors.lastname: Koekebakker
authors.forename: R D
authors.initials: RD
authors.lastname: Barr
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D006651:Histocytochemistry; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008094:Lithium / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc; D016186:Receptor, Macrophage Colony-Stimulating Factor
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D008094:Lithium; D016186:Receptor, Macrophage Colony-Stimulating Factor; D006854:Hydrocortisone