Alterations in mitogen-induced calcium mobilization and intracellular free calcium produced by 7,12-dimethylbenz(a)anthracene in the Jurkat human T cell line.
The purpose of these studies was to assess the effects of 7,12-dimethylbenz(a)anthracene (DMBA), an immunosuppressive polycyclic aromatic hydrocarbon (PAH), on Ca+2 mobilization induced by phytohemagglutinin (PHA) in the Jurkat human T cell line. Intracellular levels of free cytosolic Ca+2 were examined by flow cytometry using Indo-1 loaded cells. At doses of 3-30 microM, DMBA was found to produce a dose and time-dependent inhibition of Ca+2 mobilization in Jurkat following in vitro exposure. The decrease in Ca+2 mobilization was correlated with an increase in baseline levels of cytoplasmic free Ca+2. Two non-immunosuppressive PAH, benzo(e)pyrene and anthracene, failed to inhibit PHA-induced Ca+2 mobilization or alter baseline levels of free Ca+2. These results suggest that DMBA may produce immunosuppression by inhibiting Ca+2 mobilization or by altering Ca+2 homeostasis in activated T cells.
Burchiel
S W
SW
University of New Mexico, College of Pharmacy Toxicology Program, Albuquerque 87131.
Thompson
T A
TA
Davis
D A
DA
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D015127:9,10-Dimethyl-1,2-benzanthracene; D002118:Calcium