Triphenyltin acetate-induced cytotoxicity and CD4(+) and CD8(+) depletion in mouse thymocyte primary cultures.
Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide triphenyltin acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 microM) was cytotoxic to these cells, as demonstrated by the significant (P<0.05) reduction of the cell viability percentage (trypan blue dye exclusion test), the neutral red uptake and the reduction of tetrazolium salts to formazan products (MTT assay). These overt effects were already noticed after 4 h of exposure to TPTA. The fungicide otherwise significantly reduced, after 24 h of incubation, the percentage of mature single positive thymocytes, particularly the CD4(+)/CD8(-) one. Finally, a significative dose-dependent inhibition of the T-cell mitogen-induced cell proliferation was observed in thymocytes exposed to 1 and 8 microM TPTA. These results are indicative of the TPTA immunotoxic properties, according to previous published reports concerning the in vitro and in vivo toxicity of some di- and triorganotin compounds.
Dacasto
M
M
Dipartimento di Patologia Animale, Sezione di Farmacologia e Tossicologia, Università di Torino, via Leonardo da Vinci 44, I-10095 (Torino), Grugliasco, Italy. dacasto@veter.unito.it
Cornaglia
E
E
Nebbia
C
C
Bollo
E
E
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005659:Fungicides, Industrial / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009499:Neutral Red / Q000493:pharmacokinetics; D009947:Organotin Compounds / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism / Q000493:pharmacokinetics; D013844:Thiazoles / Q000378:metabolism / Q000493:pharmacokinetics; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014343:Trypan Blue / Q000493:pharmacokinetics
D015704:CD4 Antigens; D016827:CD8 Antigens; D005659:Fungicides, Industrial; D009947:Organotin Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D003208:Concanavalin A; D009499:Neutral Red; C011978:phentin acetate; C022616:thiazolyl blue; D014343:Trypan Blue