Abstract
The immune system can be the target of many chemicals, with potentially severe adverse effects on the host’s health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.
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Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A (2004) Pesticides and oxidative stress: a review. Med Sci Monit 10(6):141–147
Adresi Y (2003) Butyrylcholinesterase: structure and physiological importance. Turk J Biochem 28:54–61
Agrawal RC (1999) Induction of chromosomal aberrations by propoxur in mouse bone marrow cells. Biomed Environ Sci 12(4):292–5
Agrawal RC, Mehrotra NK (1997) Assessment of mutagenic potential of propoxur and its modulation by indole-3-carbinol. Food Chem Toxicol 35(10–11):1081–4
Allinson M, Kageyama S, Nakajima D, Kamata R, Shiraishi F, Goto S, Salzman SA, Allinson G (2012) A pilot survey of 39 Victorian WWTP effluents using a high speed luminescent umu test in conjunction with a novel GC-MS-database technique for automatic identification of micropollutants. Water Sci Technol 66(4):768–74
Azad GK, Singh V, Tomar RS (2014) Assessment of the biological pathways targeted by isocyanate using N-succinimidyl N-methylcarbamate in budding yeast Saccharomyces cerevisiae. PLoS One 9(3):e92993
Banks CN, Lein JA (2012) Review of experimental evidence linking neurotoxic organophosphorus compounds and inflammation. Neurotoxicology 33:575–584
Banks D, Soliman MR (1997) Protective effects of antioxidants against benomyl-induced lipid peroxidation and glutathione depletion in rats. Toxicology 116:177–81
Bemis J C, Labash C, Avlasevich S L, Carlson K, Berg A, Torous D K, Barragato M, James T, Gregor M, Dertinger S D (2015) Rat Pig-a mutation assay responds to the genotoxic carcinogen ethyl carbamate but not the non-genotoxic carcinogen methyl carbamate. Mutagenesis. In press.
Bernier J, Girard D, Krzystyniak K, Chevalier G, Trottier B, Nadeau D, Rola-Pleszczynski M, Fournier M (1995) Immunotoxicity of aminocarb. III. Exposure route-dependent immunomodulation by aminocarb in mice. Toxicology 99(1–2):135–146
Bierkens J, Maes J, Plaetse FV (1998) Dose-dependent induction of heat shock protein 70 synthesis in Raphidocelis subcapitata following exposure to different classes of environmental pollutants. Environ Pollut 101(1):91–97
Bigot-Lasserre D, Chuzel F, Debruyne ELM, Bars R, Carmichael NG (2003) Tumorigenic potential of carbaryl in the heterozygous p53 knockout mouse model. Food Chem Toxicol 41(2003):99–106
Blakley B, Brousseau P, Fournier M, Voccia I (1999) Immunotoxicity of pesticides: a review. Toxicol Indust Health 15:119–132
Buske-Kirschbaum A (2009) Cortisol responses to stress in allergic children: interaction with the immune response. Neuroimmunomodulation 16:325–32
Capcarova M, Petrovova E, Flesarova S, Dankova M, Massanyi P, Danko J (2010) Bendiocarbamate induced alterations in selected parameters of rabbit homeostasis after experimental peroral administration. Pest Biochem Physiol 98:213–218
Caroleo MC, Rispoli V, Arbitrio M et al (1996) Chronic administration of paraquat produces immunosuppression of T lymphocytes and astrocytosis in rats. Toxic Subst Mech 15:183–94
Cereser C, Boget S, Parvaz P, Revol A (2001) Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death. Toxicology 63:153–62
Cha SW, Gu HK, Lee KP, Lee MH, Han SS, Jeong TC (2000) Immunotoxicity of ethyl carbamate in female BALB/c mice: role of esterase and cytochrome P450. Toxicol Lett 115(3):173–81
Chambers J, Oppenheimer SF (2004) Organophosphates, serine esterase inhibition, and modeling of organophosphate toxicity. Toxicol Sci 77:185–187
Cheng M, Conner MK (1982) Comparison of sister chromatid exchange induction and known carcinogenic activities of vinyl and allyl carbamates. Cancer Res 42(6):2165–7
Corsini E, Sokooti M, Galli CL, Moretto A, Colosio C (2013) Pesticide induced immunotoxicity in humans: a comprehensive review of the existing evidence. Toxicology 307:123–35
Dietert RR (2008) Developmental immunotoxicity (DIT) in drug safety testing: matching DIT testing to adverse outcomes and childhood disease risk. Curr Drug Saf 3:216–226
Dong J, Lu X, Wei Y, Luo L, Dunaway-Mariano D, Carey PR (2003) The strength of dehalogenase-substrate hydrogen bonding correlates with the rate of Meisenheimer intermediate formation. Biochemistry 42(31):9482–90
Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–60
El-Bini Dhouib I, Lasram MM, Abdeladhim M, Gharbi N, Ben Ahmed M, El-Fazaa S (2014) Immunosuppression and oxidative stress induced by subchronic exposure to carbosulfan in rat spleen; Immunomodulatory and antioxidant role of N-acetylcysteine. Toxicol Mech Methods 24(6):417–27
El-Bini Dhouib I, Annabi A, Jrad A, El-Golli N, Gharbi N, Lasram MM, El-Fazaa S (2015) Carbosulfan-induced oxidative damage following subchronic exposure and the protective effects of N-acetylcysteine in rats. Gen Physiol Biophys 34(3):249–6
Femando RC, Nair J, Barbin A, Miller JA, Bartsch H (1996) Detection of 1 rA/6 -ethenodeoxyadenosine and S^-elhenodeoxycytidine by immunoaffinity/32P-postlabelling in liver and lung DNA of mice treated with ethyl carbamate (urethane) or its metabolites. Carcinogenesis 17:1711–1718
Fiore MC, Anderson HA, Hong R, Gilubjatnokov R, Seiser JE, Nordstrom D, Hanrahan L, Belluk D (1986) Chronic exposure to aldicarb-contaminated groundwater and human immune function. Environ Res 41:633–645
Freeman ML, Meredith MJ (1989) Measurement of Protein Thiols after Heat Shock Using 3-(N-Maleimido-Propionyl) Biocytin Labeled Proteins Separated by SDS-PAGE and Electroluted onto Nitrocellulose: Thiol Blotting. Radiat Res 117(2):326–333
Fukuto TR (1990) Mechanism of Action of Organophosphorus and Carbamate Insecticides. Environ Health Perspect 87:245–254
Fukuyama T, Tajima Y, Ueda H, Hayashi K, Shutoh Y, Harada T, Kosaka T (2009) Allergic reaction induced by dermal and/or respiratory exposure to low-dose phenoxyacetic acid, organophosphorus, and carbamate pesticides. Toxicology 261(3):152–161
Gao H, Wang D, Zhang S, Xu M, Yang W, Yan P, Liu Y, Luo X, Wu H, Yao P, Yan H, Liu L (2015) Roles of ROS mediated oxidative stress and DNA damage in 3-methyl- 2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of SpragueeDawley rats. Regulatory Toxicology and Pharmacology. Article in press.
Gholam S, Jorsaraei A, Maliji G, Azadmehr A, Akbar A, Moghamddamnia A, Faraji AA (2014) Immunotoxicity effects of Carbaryl In Vivo and In Vitro. Environ Toxicol Pharmacol 38(3):838–844
Giri S, Giri A, Sharma GD, Prasad SB (2002) Mutagenic effects of carbosulfan, a carbamate pesticide. Mutat Res 519:75–82
Guo TL, Chi RP, Zhang XL (2006) Modulation of immune response following dietary genistein exposure in F0 and F1 generations of C57BL/6 mice: evidence of thymic regulation. Food Chem Toxicol 44:316–25
Gupta RC, Milatovic D, Dettbarn WD (2001) Nitric oxide modulates high-energy phosphates in brain regions of rats intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N-tert-butyl-alpha-phenylnitrone or vitamin E. Arch Toxicol 75:346–56
Hajoui O, Flipo D, Mansour S, Fournier M, Krzystyniak K (1992) Immunotoxicity of subchronic versus chronic exposure to aldicarb in mice. Int J Immunopharmacol 14(7):1203–11
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–74
Handy RD, Abd-El Samei HA, Bayomy MFF, Mahran AM, Abdeen AM (2002) Chronic diazinon exposure: pathologies of spleen, thymus, blood cells, and lymph nodes are modulated by dietary protein or lipid in the mouse. Toxicology 172(5):13–34
Harboe M, Quayle AJ (1991) Heat shock proteins: friend and foe? Clin Exp Immunol 86:2–5
Ibrahim AA, Harabawy ASA (2014) Sublethal toxicity of carbofuran on the African catfish Clarias gariepinus: hormonal, enzymatic and antioxidant responses. Ecotoxicol Environ Saf 106:33–39
Jeon SD, Lim JS, Moon CK (2001) Carbofuran suppresses T-cell-mediated immune responses by the suppression of T-cell responsiveness, the differential inhibition of cytokine production, and NO production in macrophages. Toxicol Lett 119:143–155
Jeong TC, Kim HJ, Cha SW, Park JI, Shin HC, Kim DH, Han SS, Roh JK (1996) Effects of ethyl carbamate and its metabolites on the antibody response in splenocyte cultures from female BALB/c mice. Immunopharmacol Immunotoxicol 18:91–103
Jones K, Everard M, Harding A-H (2014) Investigation of gastrointestinal effects of organophosphate and carbamate pesticide residues on young children. Int J Hyg Environ Health 217(2–3):392–398
Jorsaraei SGA, Maliji G, Azadmehr A, Moghadamnia AA, Faraji AA (2014) Immunotoxicity effects of carbaryl in vivo and in vitro. Environ Toxicol Pharmacol 38(3):838–844
Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–67
Lasram MM, Bini Dhouib I, Bouzid K, Jrad Lamine A, Annabi A, Belhadjhmida N, Ben Ahmed M, El Fazaa S, Abdelmoula J, Gharbi N (2014) Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats. ETAP 38:542–53
Lawson T, Pound A (1978) Phosphate ester formation by alkyl carbamate in vivo. Proc Am Assoc Cancer Res 19:184
Li Q (2007) New mechanism of organophosphorus pesticideinduced immunotoxicity. J Nippon Med Sch 2:92–105
Li Q, Kobayashi M, Kawada T (2015) Carbamate pesticide-induced apoptosis in human T lymphocytes. Int J Environ Res Public Health 12(4):3633–45
Li Q, Nagahara N, Takahashi H, Takeda K, Okumura K, Minami M (2002) Organophosphorus pesticides markedly inhibit the activities of natural killer, cytotoxic T lymphocyte and lymphokine-activated killer: a proposed inhibiting mechanism via granzyme inhibition. Toxicology 172:181–190
Lind MH, Rozell B, Wallin RP, van Hogerlinden M, Ljunggren HG, Toftgård R (2004) Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-kappa B inhibition. Proc Natl Acad Sci 101:4972–7
Lotti M, Moretto A (1999) Promotion of organophosphateinduced delayed polyneurophathy by certain esterase inhibitors. Chem Biol Interact 120:519–524
Lotti M (1992) The pathogenesis of organophosphate polyneuropathy. Crit Rev Toxicol 21:465–487
Luebke RW, Copeland CB, Daniels M, Lambert AL, Gilmour MI (2001) Suppression of Allergic Immune Responses to House Dust Mite (HDM) in Rats Exposed to 2,3,7,8-TCDD. Toxicol Sci 62(1):71–79
Mahajan R, Blair A, Coble J, Lynch CF, Hoppin JA, Sandler DP, Alavanja MC (2007a) Carbaryl exposure and incident cancer in the Agricultural Health Study. Int J Cancer 121(8):1799–1805
Mahajan R, Blair A, Coble J, Lynch CF, Hoppin JA, Sandler DP, Alavanja MCR (2007b) Carbaryl exposure and incident cancer in the Agricultural Health Study, Int. J. Cancer 121:1799–1805
Mayne GJ, Martin PA, Bishop CA, Boermans HJ (2004) Stress and immune responses of nestling tree swallows (Tachycinet bicolor) and eastern bluebirds (Sialia sialis) exposed to nonpersistent pesticides and p, p′-dichlorodiphenyldichloroethylene in apple orchards of southern ontario, Canada. Environ Toxicol Chem 23(12):2930–2940
Medina-De la Garza CE, Guerrero-Ramírez G, García-Hernández M, Castro-Corona MA, Torres-López E, Brattig NW, Salinas-Carmona MC (2012) Immunomodulatory activity of diethylcarbamazine on humoral, cellular cytokine response and respiratory burst in BALB/c mice. Immunopharmacol Immunotoxicol 34(3):477–83
Meeker JD (2010) Exposure to environmental endocrine disrupting compounds and men’s health. Maturitas 66:236–241
Mokarizadeh A, Faryabi MR, Rezvanfar MA, Abdollahi M (2015) A comprehensive review of pesticides and the immune dysregulation: mechanisms, evidence and consequences. Toxicol Mech Methods 25(4):258–78
Monteiro M, Quintaneiro C, Pastorinho M, Pereira ML, Morgado F, Guilhermino L, Soares AMVM (2006) Acute effects of 3,4-dichloroaniline on biomarkers and spleen histology of the common goby Pomatoschistus microps. Chemosphere 62:1333–1339
Mostafalou S, Abdollahi M (2013) Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol 268:157–77
Narita S, Goldblum RM, Watson CS (2007) Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators. Environ Health Perspect 115:48–52
Nwani CD, Lakra WS, Nagpure NS, Kumar R, Kushwaha B, Srivastava SK (2010) Mutagenic and genotoxic effects of carbosulfan in freshwater fish Channa punctatus (Bloch) using micronucleus assay and alkaline single-cell gel electrophoresis. Food Chem Toxicol 48(1):202–8
Pfeiffer CJ, Qiu B, Cho CH (1997) Electron microscopic perspectives of gill pathology induced by 1-naphthyl-Nmethylcarbamate in the goldfish (Carassius auratus Linnaeus). Histol Histopathol 12(3):645–53
Pou S, Pou WS, Bredt DS et al (1992) Generation of superoxide by purified brain nitric oxide synthase. J Biol Chem 267:24173–6
Prado-Ochoa MG, Abrego-Reyes VH, Velázquez-Sánchez AM, Muñoz-Guzmán MA, Ramírez-Noguera P, Angeles E, Alba-Hurtado F (2014a) Subchronic toxicity study in rats of two new ethyl-carbamates with ixodicidal activity. Biomed Res Int 2014:467105
Prado-Ochoa MG, Gutiérrez-Amezquita RA, Abrego-Reyes VH, Velázquez-Sánchez AM, Muñoz-Guzmán MA, Ramírez-Noguera P, Angeles E, Alba-Hurtado F (2014b) Assessment of acute oral and dermal toxicity of 2 ethyl-carbamates with activity against Rhipicephalus microplus in rats. Biomed Res Int 2014:956456
Ranjbar A, Pasalar P, Abdollahi M (2002) Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesti-cide manufacturing workers. Hum Exp Toxicol 21:179–182
Rencüzogullari E, Topaktas M (1996) The effects of Marshal and its effective ingredient carbosulfan on SCE, MI and RI in cultured human lymphocytes. Turk J Biol 20:1–12
Rencüzogullari E, Topaktas M (1998) Sister chromatid exchange in cultured human lymphocytes treated with carbosulfan, ethyl carbamate, ethyl methanosulfonate separately and in mixtures. Turk J Biol 22:369–387
Rodgers KE, Leung N, Imamura T, Devens BH (1986) Rapid in Vitro Screening Assay for lmmunotoxic Effects of Organophosphorus and Carbamate Insecticides on the Generation Cytotoxic T-Lymphocyte Responses’ Pesticide biochemistry and physiology 26: 292–301 Pfeiffer CJ, Qiu B, Cho CH (1997) Electron microscopic perspectives of gill pathology induced by 1-naphthyl-N-methylcarbamate in the goldfish (Carassius auratus Linnaeus). Histol Histopathol 12(3):645–53
Seth V, Banerjee BD, Chakraborty AK, Institoris L, Desi I (2002) Effect of propoxur on humoral and cell-mediated immune responses in albino rats. Bull Environ Contam Toxicol 68(3):369–76
Sharova LV, Gogal RM, Sharov AA, Chrisman MV, Holladay SD (2002) Immune stimulation in urethane-exposed pregnant mice increases expression level of spleen leukocyte genes for TGFβ3 GM-CSF and other cytokines that may play a role in reduced chemical-induced birth defects. Int Immunopharmacol 2(10):1477–1489
Singh SK, Bano F, Mohanty B (2015) Vitamin E pretreatment prevents the immunotoxicity of dithiocarbamate pesticide mancozeb in vitro: a comparative age-related assessment in mice and chick. Pestic Biochem Physiol. In press
Singhal LK, Bagga S, Kumar R, Chauhan RS (2003) Down regulation of humoral immunity in chickens due to carbendazim. Toxicol In Vitro 17(5–6):687–92
Soloneski S, Kujawski M, Scuto A, Larramendy ML (2015) Carbamates: a study on genotoxic, cytotoxic, and apoptotic effects 4 induced in Chinese hamster ovary (CHO-K1) cells. Toxicol In Vitro. In press
Song X, Tian H, Bressler J, Pruett S, Pope C (2002) Acute and Repeated Restraint Stress Have Little Effect on Pyridostigmine Toxicity or Brain Regional Cholinesterase Inhibition in Rats. Toxicol Sci 69(1):157–164
Tanriverdi F, Silveira LF, MacColl GS, Bouloux PM (2003) The hypothalamic-pituitary-gonadal axis: immune function and autoimmunity. J Endocrinol 176:293–304
Theus SA, Tabor DR, Gand JY, Barnett JB (1993) Alteration of Macrophage Cytotoxicity through Endogenous Interferon and Tumor Necrosis Factor α Induction by Propanil. Toxicol Appl 118:46–52
Vial T, Nicolasa B, Descotesa J (1996) Clinical immunotoxicity of pesticides. J Toxicol Environ Health 48:215–229
Vidyasagar J, Karunakar N, Reddy MS, Rajnarayana K, Surender T, Krishna DR (2004) Oxidative stress and antioxidant status in acute organophosphorous insecticide poisoning. Indian J Pharmacol 36:76–79
Wang Z, Wilhelmsson C, Hyrsl P, Loof TG, Dobes P, Klupp M, Loseva O, Mörgelin M, Iklé J, Cripps RM, Herwald H, Theopold U (2010) Pathogen entrapment by transglutaminase — a conserved early innate immune mechanism. PLoS Pathogens 6(2):e1000763
Whalen MM, Loganathan BG, Yamashita N, Saito T (2003) Immunomodulation of human natural killer cell cytotoxic function by triazine and carbamate pesticides. Chem Biol Interact 145:311–319
Wiedenmann D, Stehrerer-Schmide P, Wolf HU (1990) Mutagenic effects of carbosulfan and furathiocarb in the Ames test and Yeast assay, in: Proceedings of the 31st Spring Meeting of the Deutsche Gesellschaft für Pharmakologische Toxicologie (German Society for Pharmacology and Toxicology), Mainz, West Germany, 13–16 March, Naunyn Schmiedeberg’s Arch. Pharmacol. Suppl. 341 R 29
Williams CV, Fletcher K, Tinwell H, Ashby J (1998) Mutagenicity of ethyl carbamate to lacZ- transgenic mice. Mutagenesis 13:133–137
Yang ZP, Dettbarn WD (1996) Diisopropylphosphorofluoridate induced cholinergic hyperactivity and lipid peroxidation. Toxicol Appl Pharmacol 138:48–53
Yoon JY, Oh SH, Yoo SM, Lee SJ, Lee HS, Choi SJ, Moon CK, Lee BH (2001) N-Nitrosocarbofuran, but not Carbofuran, induces apoptosis and cell cycle arrest in CHL cell. Toxicology 169(2):153–61
Zhao M, Chen F, Wang C, Zhang Q, Gan J, Liu W (2010) Integrative assessment of enantio selectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids. Environ Pollut 158:1968–1973
Zhou C, Tabb MM, Nelson EL (2006) Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. J Clin Invest 116:2280
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Dhouib, I., Jallouli, M., Annabi, A. et al. From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system. Environ Sci Pollut Res 23, 9448–9458 (2016). https://doi.org/10.1007/s11356-016-6418-6
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DOI: https://doi.org/10.1007/s11356-016-6418-6