Immunomodulatory Effects of Tetrachlorobenzoquinone, a Reactive Metabolite of Hexachlorobenzene

Abstract

Hexachlorobenzene (HCB) is an environmental pollutant that causes autoimmune-like effects in humans and rats. It is not completely clear whether T cells are involved and, if so, how they are stimulated after oral exposure to HCB. HCB as a rather inert chemical is not likely to bind covalently to macromolecules. The oxidative metabolite of HCB, tetrachlorobenzoquinone (TCBQ), which is in a redox equilibrium with tetrachlorohydroquinone (TCHQ), can bind to macromolecules, hence may form hapten-carrier complexes in vivo. We have assessed in the reporter antigen-popliteal lymph node assay whether HCB or TCHQ and TCBQ are able to induce a 2,4,6-trinitrophenyl (TNP) specific IgG1 response to the T cell-independent antigen TNP-Ficoll, which is indicative of neoantigen specific T cell help. To this end, these compounds and silica were injected into the footpad of Balb/c mice. Silica was included as an inert model compound, which causes autoimmune-like effects by activating macrophages. Seven days later, cell number and TNP specific antibody-secreting cells (ASC) in the popliteal lymph node (PLN) were determined. Furthermore, a secondary PLNA was performed to find out if TCHQ was capable of eliciting a memory response. Silica, TCHQ, and TCBQ, but not HCB, increased PLN cellularity and the number of IgM-producing ASC by ELISPOT. Both oxidative metabolites were able to induce the formation of germinal centers as assessed by immunohistochemistry and an IgG1 response to TNP-Ficoll. In the secondary PLNA, only mice primed with TCHQ and challenged with TCHQ together with TNP-Ficoll showed a significant increase in TNP specific IgG1 ASC. Present data show that TCHQ and TCBQ are capable of inducing neoantigen specific T cell help and that TCHQ can induce a compound specific memory response.

Antibrush Border Antibody Disease: A Case Report and Literature Review

“…The trigger for the production of ABBA is unknown, although it may be associated with other autoimmune diseases and chronic infections. [13][14][15][16][17][18][19][20][21][22][23] Our patient had no previous history of autoimmunity, but there was history of mycobacterial infection and occupational exposure to silica and pesticides. Mycobacterial infections are involved in J o u r n a l P r e -p r o o f mechanisms of "molecular mimicry" and consequent autoimmunity through cross reaction; therefore, it is possible that they are involved in the pathogenesis of diseases such as primary biliary cirrhosis, sarcoidosis, and systemic lupus erythematosus (SLE).…”

“…demonstrated that hexachlorobenzene led to the formation of lymph node germinal centers in mice, with an expressive increase in B-cell and T-cell subpopulations. 21 Serologies are non-diagnostic of ABBA disease. 22 Diagnostic confirmation occurs by kidney biopsy.…”

“…A study performed in 1993 demonstrated that hexachlorobenzene, another pesticide, induces increased levels of autoantibodies such as anti-DNA and rheumatoid factor in animal models. 20 Ten years later, Ezendam et al 21 demonstrated that hexachlorobenzene led to the formation of lymph node germinal centers in mice, with an expressive increase in B-cell and T-cell subpopulations.…”

Mechanism of teratogenesis: Electron transfer, reactive oxygen species, and antioxidants

“…Due to space limitations, we mention a number of other compounds, accompanied by references dealing with their reproductive toxicity and mechanisms, but without discussion: vitamin A congeners (Kovacic and Jacintho, 2001b), N‐nitroso compounds (Kovacic and Jacintho, 2001b; Prater et al, 2006) hexachlorobenzene (Ezendam et al, 2003), 1,3‐dichloropropene (Kovacic and Becvar, 2000; Eder et al, 2006), ethoxyethanol (Kovacic and Jacintho, 2001b; Johnson, 2002), polynuclear aromatic hydrocarbons (Kovacic and Jacintho, 2001a; Parman and Wells, 2002; Kasapinovic et al, 2004; Park et al, 2006), formaldehyde (Halliwell and Gutteridge, 1999, pp. 548–553; Thrasher and Kilburn, 2001), carbon monoxide (Alexander and Tuan, 2003; Kovacic and Somanathan, 2005), bromates (Murata et al, 2001; Chipman et al, 2006), and plant toxins (Knight and Walter, 2004; Kovacic and Somanathan, 2005).…”

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

“…PAHs and benzene are established environmental genotoxins, whereas organochlorides and heavy metals are known to produce free radicals and thereby lead to oxidative DNA damage, and thus represent a cancer risk (3)(4)(5)(6)(7). To elucidate the genotoxic effects of these exposures among the Flemish populations, DNA damage levels as measured by the Comet assay and as micronuclei in lymphocytes, urinary 8-hydroxydeoxyguanosine and several serum tumor markers were analyzed.…”