Immunosuppression induced by 7,12-Dimethylbenz(A)anthracene (DMBA)in AIRmax and AIRmin mice that exhibit polymorphism in the AhR gene

• Grant number: 16/09803-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2016
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Orlando Garcia Ribeiro Filho
• Grantee: Nathalia Magalhães de Andrade
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are aggressive factors found in the environment, with potential carcinogenic and immunotoxic for humans and other species. Among the damage caused by PAHs are those that directly affect the proliferative dynamics of hematopoietic cells. A synthetic prototype of PAH used in research is the 7.12 - dimethylbenzanthracene (DMBA), whose proven biological effects in mice are immunosuppression, myelotoxicity and oncogene activation. The toxicity of DMBA depends on binding to Aryl hydrocarbon receptor (AHR), which triggers a cascade of intracellular events that ultimately lead to transformation of DMBA into toxic metabolites. However, the effect of these receptors activation varies due to functional polymorphisms found in the Ahr gene, which determines Ahr alleles of high (Ahrb1) and low affinity (Ahrd) for PAHs. In two lines of mice phenotypically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to non-immunogenic substance was observed segregation of Ahrd and Ahrb1 alleles in AIRmax and AIRmin lineages respectively. Regarding toxic effects of DMBA on bone marrow cells, the AIRmin mice develop cell cycle blockage, deficiency in myeloid differentiation and myelodysplasia, effects whose may be associated with Ahr gene polymorphism. Given these results, it is likely that there is also heterogeneity in the specific immune response of the antibody production due to the suppressive effects on lymphoid population of the bone marrow. Therefore, our aim is to investigate the humoral suppression mechanisms of specific immune response triggered by treatment with polycyclic aromatic hydrocarbon, DMBA, in the context of AIRmax and AIRmax mouse stocks.