Changes in sensitivity to anticancer drugs during TPA-induced cellular differentiation in a human T-lymphoblastoid cell line (MOLT-4).
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.
Takimoto
T
T
Department of Pediatrics, Kyoto University, Japan.
Kubota
M
M
Tsuruta
S
S
Kitoh
T
T
Tanizawa
A
A
Akiyama
Y
Y
Kiriyama
Y
Y
Mikawa
H
H
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
D000970:Antineoplastic Agents; D013755:Tetradecanoylphorbol Acetate