Avaliação da modulação por 7,12-Dimetilbenzantraceno (DMBA) da capacidade proliferativa de células T em camundongos airmax e airmin com gamaglobulina humana (HGG)

Abstract

Polycyclic aromatic hydrocarbons (HPAs) are a class of substances widely distributed in the environment, many of which have toxic and carcinogenic potential for different species, including humans. 7,12-Dimethylbenzanthracene (DMBA) is a synthetic prototype of HPA. Among the various effects, these xenobiotics cause cytotoxicity, genotoxicity and, consequently, carcinogenesis and immunosuppression, according to results obtained experimentally in murine models. Mice treated with DMBA show marked decrease in T cell-mediated cytotoxicity, proliferative response to T-dependent mitogen and induction of cytokine production. The toxicity of DMBA is associated with the binding of this compound to the Aryl Hydrocarbon receptor (Ahr) whose binding triggers a series of intracellular events. The effects of activation of these receptors vary due to polymorphisms found in the Ahr gene. In murine model, these variations are closely associated with high Ahr alleles (Ahrb1) or low (Ahrd) affinity for HPAs. In two lines of mice phenotypically selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory response to the non-immunogenic substance, segregation of the Ahrd and Ahrb1 alleles was observed in AIRmax and AIRmin mice, respectively. With respect to the toxic effects of DMBA on the bone marrow, AIRmin animals develop blockage in the cell cycle, deficiency in myeloid differentiation and myelodysplasia, effects associated with Ahr gene polymorphism. Therefore, the objective of the work is to investigate the quantitative antibody production and proliferative capacity of T cells from animals immunized with HGG. We observed a modulation of the production of anti-HGG antibodies in the secondary response at doses of 12,5 and 25mg/kg body weight. Concerning the inhibition of proliferation, no significant effect was observed either on the specific proliferation with HGG or ConA. These results have shown, to date, that the modulation of the cellular response has not been affected by the depletion by the DMBA treatment, however DMBA may interfere with the antibody production function by B cells.