Aflatoxin B-1 residues in human livers and their relationship with markers of hepatic carcinogenesis in Sao Paulo, Brazil

Autor(es)

Ramalho, Leandra N. Z. ^[1] ; Porta, Livia D. ^[1] ; Rosim, Roice E. ^[2] ; Petta, Tania ^[3] ; Augusto, Marlei J. ^[1] ; Silva, Deisy M. ^[1] ; Ramalho, Fernando S. ^[1] ; Oliveira, Carlos A. F. ^[2]

Afiliação do(s) autor(es)

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

^[2] Univ Sao Paulo, Sch Anim Sci & Food Engn, Dept Food Engn, Ave Duque de Caxias Norte 225, BR-13635900 Pirassununga, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGY REPORTS; v. 5, p. 777-784, 2018.
• Citações Web of Science: 5

Resumo

In this study, hepatic biopsies from autopsy cases in Sao Paulo, Brazil, showing hepatocellular carcinoma (HCC, n = 8), cirrhosis associated with viral hepatitis (VC, n = 20), cirrhosis associated with alcoholism (AC, n = 20), and normal livers (NL or controls, n = 10) were subjected to determination of aflatoxin B-1 (AFB(1)) and its main metabolites, and of markers of hepatic carcinogenesis Only non-metabolized AFB(1) was detected in 13 samples (27.1%, N = 48) of liver disorders (HCC, VC and AC), at levels between 10.0 and 418.0 pg/g (mean: 76.6 +/- 107.7 pg/g). Immuno-labeling of p53, cyclin D1, p21, beta-catenin, and Prohibitin (PB) increased mainly in HCC patients, in relation to the controls. AFB(1)+ samples of HCC presented higher expressions of p53, cyclin D1, p21, and beta-catenin compared with AFB(1)-livers. In contrast, p27, p16, and Rb immuno-labeling decreased in HCC, VC, and AC samples, compared with NL, with lowest values in AFB(1)+ samples for all liver disorders. Compared with NL, gene expression of cyclin D1 and PB in AFB(1)+ samples of HCC and AC were also higher, along with higher gene expression of p21 in VC and AC AFB(1)+ livers. Results indicated that patients with liver disorders were exposed to dietary aflatoxins, and that residual AFB(1) in liver negatively affected the p53 and protein Rb pathways in HCC. Moreover, the presence of AFB(1) in cirrhotic livers warrants concern about the potential contribution of dietary aflatoxin to disease progression during VC and AC. (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