title: Synergism between phorbol myristate acetate and calcium ionophore in inducing proliferation of in vitro γ-irradiated murine lymphocytes.
abstract: The objective of this study was to analyze the in vitro effects of γ-irradiation (0-5 Gy) on lymphocyte proliferation in animals sensitive to radiation as BALB/c mice. Lymphocytes were irradiated and underwent different treatments: quiescent cells were cultured with calcium ionophore A23187 (5 min or 48 h) with or without phorbol myristate acetate (PMA); lymphocytes (control cells or incubated with A23187 and PMA) were also cultured with four mitogens that are specific to the different subpopulations to determine the degree of inhibition of the response to radiation. Results obtained indicated that in quiescent cells, A23187 and PMA treatment had a mitogenic effect, which peaked with long A23187 treatment (48 h); synergism was further demonstrated between both drugs and was enhanced with higher ionizing radiation doses. However, in both irradiated and non-irradiated mitogen-stimulated cells, A23187 (48 h) and PMA had a strong inhibitory effect on cell proliferation. In conclusion these results indicate that irradiated BALB/c mice lymphocytes respond to treatment with A23187 and PMA more actively than controls. Inhibition of the post-exposure mitogen-induced proliferative response and the synergic effect between A23187 and PMA also suggest altered PKC activation mechanisms in cell membranes. Comparing with previous studies with in vivo irradiated mice, the effects of IR in vitro were less intense.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Hernández-Godoy
authors.forename: Dolores
authors.initials: D
authors.lastname: Planelles
authors.forename: Baltasar
authors.initials: B
authors.lastname: Balsalobre
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000008:administration & dosage*; D061207:Calcium Ionophores / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D005260:Female; D005720:Gamma Rays; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011836:Radiation Tolerance / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
chemical_list: D061207:Calcium Ionophores; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate