title: Changes in sensitivity to anticancer drugs during TPA-induced cellular differentiation in a human T-lymphoblastoid cell line (MOLT-4).
abstract: After four days of treatment with 10(-8) M TPA, differentiation of the human T-lymphoblastoid cell line MOLT-4 was induced along the T cell lineage, confirmed by a fall in adenosine deaminase and 5'-ectonucleotidase and a rise in purine nucleoside phosphorylase activity. TPA-treated cells became resistant to the cytotoxic effects of 1-beta-D-arabinofuranosylcytosine (Ara-C), 9-beta-D-arabinofuranosyladenine (Ara-A), and 2-chlorodeoxyadenosine. This was, in part, due to the altered cell cycle distribution (accumulation of cells in the G1 phase), since the toxicity of Ara-C and Ara-A is S phase specific. The diminished rate of Ara-C transport concomitant with Ara-CTP formation after TPA treatment is considered to be the biochemical basis for this acquired resistance.
authors.affiliation: Department of Pediatrics, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takimoto
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: S
authors.initials: S
authors.lastname: Tsuruta
authors.forename: T
authors.initials: T
authors.lastname: Kitoh
authors.forename: A
authors.initials: A
authors.lastname: Tanizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Kiriyama
authors.forename: H
authors.initials: H
authors.lastname: Mikawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004351:Drug Resistance; D006801:Humans; D007945:Leukemia, Lymphoid / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D013755:Tetradecanoylphorbol Acetate