Abstract A40: Induction of oxidative/nitrosative stress, proinflammatory cytokines and dysregulation of Wnt/beta-catenin signaling by benzo(a)pyrene in colons of BALB/c mice

Abstract

Abstract Epidemiologic surveys and experimental data have revealed that environmental and dietary factors contribute to the etiology of colon cancer, which ranks third in cancer-related mortalities in the United States and fourth worldwide. In particular, human diet containing environmental carcinogens such as benzo(a)pyrene (B(a)P), a polycyclic aromatic hydrocarbon, has been the focus of investigators recently in relation to generated interest in looking at how it exerts its colorectal cancer. The present study investigated the effects of B(a)P on biomarkers of oxidative stress, inflammation and Wnt-signaling in colon of BALB/c mice following exposure to varying doses of 62.5, 125, and 250 mg/kg B(a)P for 7 days by oral gavage. Exposure to B(a)P induced marked oxidative stress accompanied by decrease in the colonic antioxidant enzyme activities and glutathione level with concomitant increase in myeloperoxidase activity, nitric oxide, and lipid peroxidation levels. Colon histopathology results showed B(a)P-related lesions characterized by atrophy, mucosal ulceration, and gland erosion in the mice. Immunohistochemistry analysis showed that B(a)P treatment increased the protein expression of nuclear factor kappa B, proinflammatory cytokines, namely tumor necrosis factor alpha and interleukin-1 β, as well as cyclooxygenase-2 and inducible nitric oxide synthase in the mice colon. Altered canonical Wnt signaling was confirmed by strong diaminobenzidine staining for p38 mitogen-activated protein kinase, b-catenin expression, and absence of adenomatous polyposis coli following B(a)P administration. Overall, our results show that exposure of mice to B(a)P induces colonic toxicity by mechanism involving oxidative and nitrosative stress, inflammation, and dsyregulation of Wnt/b-catenin signaling, and emphasizes the role of environmental polycyclic aromatic hydrocarbons like B(a)P in the pathology of colonic toxicity and tumorigenesis. Citation Format: Ebenezer O. Farombi, Babajide O. Ajayi, Isaac A. Adedara, Solomon E. Owumi. Induction of oxidative/nitrosative stress, proinflammatory cytokines and dysregulation of Wnt/beta-catenin signaling by benzo(a)pyrene in colons of BALB/c mice [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A40.