Abstract
The effects of 3,3′,4,4′-tetrachloroazoxy-benzene (TCAOB) on the immune system of mice was examined and compared with cyclophosphamide (CY). This chemical can be produced as a result of microbial degradation of commonly used chloroaniline herbicides. Herbicides of the acylan-iline class generally have a low mammalian toxicity while remaining relatively inexpensive. Therefore, TCAOB could be formed anywhere in the environment where choroaniline pesticides are used. TCAOB treatment caused thymic atrophy and a decrease in white blood cell (WBC) count after sheep red blood cell (SRBC) immunization. A decline in the number of Lyt-1+ cells (T-helper lymphocytes) was seen in all TCAOB animals, with unimmunized mice also showing a decreased number of Lyt-2.2+ cells (T-suppressor lymphocytes). No change was found in the ratio of these two cell types. TCAOB did, however, result in a severe reduction in the number of plaque-forming-cells (PFCs) and in serum antibody concentration. CY caused a decrease in thymus weight, WBC count, the number of cells recovered per spleen, and the relative percentages of Lyt-l+ and Lyt-2.2+ cells recovered. The mice exhibited a lower lymphocyte blastogenic response to lipopolysaccharide (LPS) than control animals, but no change in Concanavalin A (Con-A) responsiveness. CY also resulted in a severe drop in the number of PFCs and the quantity of antibody produced following SRBC immunization.
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Andersson J, Sjöberg O, Möller G (1972) Mitogens as probes for immunocyte activation and cellular cooperation. Transplant Rev 11:131–177
Brock N, Gross R, Hohorst HJ, Klein HO, Schneider B (1971) Activation of cyclophosphamide in man and animals. Cancer 27:1512–1529
Cantor H, Boyse EA (1975) Functional subclasses of T lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med 141:1376–1389
Conrath TB, Coupe NB (1978) Handbook of Manual Microtiter Procedures, 2nd edn, Whittfriars Press, London
Cunningham AJ, Szenberg A (1968) Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology 14:599–600
Cupps TR, Edgar LC, Fauci AS (1982) Suppression of human B lymphocyte function by cyclophosphamide. J Immunol 128(6):2453–2457
Foley GE, Friedman OM, Drolet BP (1961) Studies on the mechanism of action of cytoxan. Evidence of activationin vivo andin vitro. Cancer Res 21:57–63
Fox BA, Westrick PW, Oh HK, Dienst SG (1983) Effect of immunosuppression on murine responses to skin allografts and Concanavalin-A: Analysis of T-cell subsets. Transplant Proc 15(3): 1988–1992
Gill JL (1978) Design and Analysis of Experiments in the Animal and Medical Sciences, Vol 1. Iowa State University Press, Ames, Iowa
Hsia MTS (1981) Mammalian toxicology of 3,3′,4,4′-tetrachlo-roazobenzene and 3,3′,4,4′-tetrachloroazoxybenzene: Implications in environmental and occupational health. In: Khan MAQ, Stanton RH (eds) Toxicology of Halogenated Hydrocarbons: Health and Ecological Effects. Pergamon Press, Oxford, pp 146–160
Hsia MTS, Burant CF (1979) Preparation and spectral analysis of 3,3′,4,4′-tetrachloroazobenzene and the corresponding azoxy and hydrazo analogs. J Assoc Offic Anal Chem 62:746–750
Hsia MTS, Burant CF, Kreamer BL, Schrankel KR (1982) Thymic atrophy induced by acute exposure of 3,3′,4,4′-te-trachloroazobenzene and 3,3′,4,4′-tetrachloroazoxybenzene in rats. Toxicology 24:231–244
Huber B, Cantor H, Shen FW, Boyse EA (1976) Independent differentiative pathways of Ly-1 and Ly-23 subclasses of T cells. Experimental production of mice deprived of selected T-cell subclasses. J Exp Med 144:1128–1133
Kaufman DD, Plimmer JR, Iwan J, Klingebiel UI (1972) 3,3′,4,4′-tetrachloroazoxybenzene from 3,4-dichloroaniline in microbial culture. J Agric Food Chem 20:916–919
Ledbetter JA, Rouse RV, Spedding-Micklem H, Herzenberg LA (1980) T cell subclasses defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med 152:280–295
McConnell EE, Moore JA (1979) Toxicopathology characteristics of the halogenated aromatics. Anal NY Acad Sci 320:138–150
Morse DL, Baker EL, Kimbrough RD, Wisseman CL (1979) III. Propanil-chloracne and rnethomyl toxicity in workers of a pesticide manufacturing plant. Clin Toxicol 15:13–21
Murphy DB, Shreffler DC (1975) Cross-reactivity between H-2K and H-2D products. I. Evidence for extensive and reciprocal serological cross-reactivity. J Exp Med 141:374–391
Nagarkatti PS, Sweeney GD, Gauldie J, Clark DA (1984) Sensitivity to suppression of cytotoxic T cell generation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on the Ah genotype of the murine host. Tox Appl Pharmacol 72:169–176
Okey AB, Bondi GP, Mason ME, Kahl GF, Eisen HJ, Guenthner TM, Nebert DW (1979) Regulatory gene product of the Ah locus. Characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation. J Biol Chem 254:11636–11648
Otterness IG, Chang YH (1976) Comparative study of cyclo-phosphamide, 6-mercaptopurine, azathiopurine and methotrexate. Relative effects on the humoral and the cellular immune response in the mouse. Clin Exp Immunol 26:346–354
Poland A, Glover E (1980) 2,3,7,8-tetrachlorodibenzo-p-dioxin; Segregation of toxicity with the Ah locus. Mol Pharmacol 17:86–94
Poland A, Greenlee WF, Kende AS (1979) Studies on the mechanism of action of the chlorinated dibenzo-p-dioxins and related compounds. Anal NY Acad Sci 320:214–230
Schrankel KR, Kreamer BL, Hsia MTS (1982) Embryotoxicity of 3,3′,4,4′-tetrachloroazobenzene and 3,3′,4,4′-tetrachlo-roazoxybenzene in the chick embryo. Arch Environ Contam Toxicol 11:195–202
Schwartz A, Askenase PW, Gershon RK (1978) Regulation of delayed-type-hypersensitivity reactions by cyclophosphamide-sensitive T-cells. J Immunol 121(4):1573–1577
Shand FL, Liew FY (1980) Differential sensitivity to cyclophos-phamide of helper T cells for humoral responses and suppressor T cells for delayed-type hypersensitivity. Eur J Immunol 10:480–483
Sharma RP, Gehring PJ (1979) Effects of 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) on splenic lymphocyte transformation in mice after single and repeated exposures. Anal NY Acad Sci 320:487–497
Silkworth JB, Grabstein EM (1982) Polychlorinated biphenyl immunotoxicity: Dependence on isomer planarity and the Ah gene complex. Toxicol Appl Pharmacol 65:109–115
Silkworth JB, Loose LD (1981) Assessment of environmental contaminant-induced lymphocyte dysfunction. Environ Health Perspect 39:105–128
Stevenson HC, Fauci AS (1980) Activation of human B lympho-cytes. XII. Differential effects ofin vitro cyclophosphamide on human lymphocyte subpopulations involved in B-cell activation. Immunology 39:391–397
Still GG, Herrett RA (1976) Methylcarbamates, carbamates, and acrylanilides. In: Kearney PC, Kaufman DD (eds) Herbicides, Degradation, and Mode of Action, Volume 2, Marcel Dekker, New York, pp 609–664
Stockman GD, Heim LR, South MA, Trentin JJ (1973) Differential effects of cyclophosphamide on the B and T cell compartments of adult mice. J Immunol 110(l):277–282
Sundström G, Jansson B, Renberg L (1978) Determination of the toxic impurities 3,3′,4,4′-tetrachloroazobenzene and 3,3′,4,4′-tetrachloroazoxybenzene in commercial diuron, linuron and 3,4-dichloroaniline samples. Chemosphere 12:973–979
Taylor JS, Wuthrich RC, Lloyd RM, Poland A (1977) Chloracne from manufacture of a new herbicide. Arch Dermatol 113:616–619
Turk JL, Parker D (1982) Effect of cyclophosphamide on immunological control mechanisms. Immunol Rev 65:99–113
Vecchi A, Sironi M, Canegrati MA, Recchia M, Garattini S (1983) Immunosuppressive effects of 2,3,7,8-tetrachlorodi-benzo-p-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase. Toxicol Appl Pharmacol 68:434–441
Vos JG, Moore JA, Zinkl JG (1973) Effect of 2,3,7,8-tetrachlo-rodibenzo-p-dioxin on the immune system of laboratory animals. Environ Health Perspect 5:149–162
Winkelstein A (1973) Mechanisms of immunosuppression: Effects of cyclophosphamide on cellular immunity. Blood 41(2):273–283
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Bleavins, M.R., Hinsdill, R.D., Hochstein, J.R. et al. Effects of 3,3′,4,4′-tetrachloroazoxybenzene on selected immune parameters of the mouse. Arch. Environ. Contam. Toxicol. 14, 669–676 (1985). https://doi.org/10.1007/BF01055773
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DOI: https://doi.org/10.1007/BF01055773