Oncogenic and tumor suppressor pathways in subchronic aflatoxicosis in rats: Association with serum and urinary aflatoxin exposure biomarkers

Autor(es)

Apolinario, Leticia A. ^[1] ; Ramalho, Leandra N. Z. ^[1] ; Moosavi, Motahareh Hashemi ^[2] ; Jager, V, Alessandra ; Augusto, Marlei J. ^[1] ; Trotta, Mauricio R. ^[1] ; Petta, Tania ^[3] ; Khaneghah, Amin Mousavi ^[4] ; Oliveira, Carlos A. F. ^[5] ; Ramalho, Fernando S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pathol & Legal Med, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Shahid Beheshti Univ Med Sci, Fac Nutr Sci & Food Technol, Natl Nutr & Food Technol Res Inst, Dept Food Sci & Technol, Tehran - Iran

^[3] Actinobac Agrosci Supera Parque Inovacao & Tecnol, Av Dra Nadir Aguiar 1805, BR-14056680 Ribeirao Preto, SP - Brazil

^[4] Univ Campinas UNICAMP, Fac Food Engn, Dept Food Sci, R Monteiro Lobato 80, BR-13083862 Campinas, SP - Brazil

^[5] Univ Sao Paulo, Sch Anim Sci & Food Engn, Dept Food Engn, Av Duque de Caxias Norte 225, BR-13635900 Pirassununga, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Food and Chemical Toxicology; v. 153, JUL 2021.
• Citações Web of Science: 0

Resumo

In this study, the changes in oncogenic and tumor suppressor signaling pathways in liver and their association with serum and urinary biomarkers of aflatoxin exposure were evaluated in Wistar rats fed diets containing aflatoxin B-1 (AFB(1)) for 90 days. Rats were divided into four groups (n = 15 per group) and assigned to dietary treatments containing 0 (control), 50 (AFB50), 100 (AFB100) and 200 mu g AFB(1) kg(-1) diet (AFB200). Multiple preneoplastic foci of hepatocytes marked with glutathione-S-transferase-placental form (GST-P) were identified in AFB100 and AFB200 groups. Hepatocellular damage induced by AFB(1) resulted in overexpression of cyclin D1 and beta-catenin. The liver expression of retinoblastoma (Rb) and p27(Kip1) decreased in AFB100 and AFB200 groups, confirming the favorable conditions for neoplastic progression to hepatocellular carcinoma. All samples from rats fed AFB(1)-contaminated diets had quantifiable AFB(1)-lysine in serum or urinary AFM(1) and AFB(1)-N-7-guanine, with mean levels of 20.42-50.34 ng mL(-1), 5.31-37.68 and 39.15-126.37 ng mg(-1) creatinine, respectively. Positive correlations were found between AFB(1)-lysine, AFM(1) or AFB(1)-N-7-guanine and GST-P+, beta-catenin+ and cyclin D1+ hepatocytes, while Rb + cells negatively correlated with those AFB(1) exposure biomarkers. The pathways evaluated are critical molecular mechanisms of AFB(1)-induced hepatocarcinogenesis in rats. (AU)

• Processo FAPESP: 10/20895-4 - Avaliação de adutos AFB1-Lisina e AFB1-N7-guanina como biomarcadores de exposição humana e animal às aflatoxinas
• Beneficiário: Carlos Augusto Fernandes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Temático