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Suppression of humoral and cellular immune response by 7,12-dimethylbenz (a) anthracene (DMBA) in AIRmax and AIRmin mice: correlation with AhR gene polymorphism

Grant number: 19/07203-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Orlando Garcia Ribeiro Filho
Grantee:Natacha Diesca dos Santos
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Polycyclic aromatic hydrocarbons (PAHs) are aggressive factors found in the environment with potential carcinogenic and immunotoxic effects for humans and other species. Among the damages caused by PAHs we stand out those that directly affect the proliferative dynamics of hematopoietic cells. A prototype of PAH largely used in experimental research is 7.12 - dimethylbenzanthracene (DMBA), whose biological effects produce 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 lead to the transformation of DMBA into toxic metabolites. The effect of DMBA depends on the functional polymorphism of the Ahr gene, Ahrb1 and Ahrd alleles, that encode the high and low AHR affinity, respectively. Two lines of mice phenotypically selected for high (AIRmax) or low (AIRmin) acute inflammatory response to non-immunogenic substance have the Ahrd and Ahrb1 alleles fixed in AIRmax and AIRmin mice, respectively. The toxic effects of DMBA on AIRmin bone marrow cells cause cell cycle blockage, deficiency in myeloid cell differentiation and myelodysplasia. This information led us to suppose that DMBA should probably impairs the specific immune response due to suppressive effects on lymphoid population. Therefore, our goal in this project is to investigate a possible humoral and/or cellular immune response suppression induced by DMBA in Human Gamma Globulin immunized AIRmax and AIRmax mice.

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