Avaliação da diferenciação das células da medula óssea de camundongos AIRmax e AIRmin tratados com DMBA e/ou crotoxina

Abstract

The development of leukemic is related to environmental and genetic factors. When exposed to aromatic hydrocarbons (PAH), such as the carcinogen and immunosuppressant 7,12-dimethylbenz(a)anthracene (DMBA), the individuals can develop neoplasias. The objective of the present study was to investigate the modulatory effects of crotoxin under the action of DMBA in the bone marrow of mice of the AIR lines. Crotoxin is the main component of Crotalus durrissus terrificus venom, responsible for high toxicity, and has an immunomodulatory, anti-inflammatory, and analgesic effect with significant therapeutic potential. In this work, we used mice phenotypically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response and that have low (Ahrd) or high (Ahrb1) affinity alleles of the aryl hydrocarbon receptor (AHR), conferring resistance or susceptibility to the risk of developing cancer. Mice were treated intraperitoneally with 50mg/kg DMBA and subcutaneously with 54μg/kg of Crotoxin and after 48 hours, bone marrow cells were obtained for total and differential counts. The results showed that DMBA treatment caused the depletion of immature neutrophil and monocyte bone marrow populations only in AIRmin mice. The administration of crotoxin provided a recovery of these populations in these mice. The results also showed the importance of the polymorphism of the Ahr gene concerning resistance or susceptibility to PAHs, suggesting an inhibition of the cell cycle by DMBA and a reversal of this effect by Crotoxin. Thus, new approaches should be explored to evaluate the DMBA's role in the cell cycle of different cell populations and the role of Crotoxin as a protector action.