| Autor: |
Ramalho LNZ; Department of Pathology, School of Medicine at Ribeirão Preto, University of São Paulo, Av. do Café, s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil., Porta LD; Department of Pathology, School of Medicine at Ribeirão Preto, University of São Paulo, Av. do Café, s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil., Rosim RE; Department of Food Engineering, School of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias - Norte, 225, CEP 13635-900, Pirassununga, SP, Brazil., Petta T; Department of Biochemistry and Immunology, School of Medicine at Ribeirão Preto, University of São Paulo, Av. do Café, s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil., Augusto MJ; Department of Pathology, School of Medicine at Ribeirão Preto, University of São Paulo, Av. do Café, s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil., Silva DM; Department of Pathology, School of Medicine at Ribeirão Preto, University of São Paulo, Av. do Café, s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil., Ramalho FS; Department of Pathology, School of Medicine at Ribeirão Preto, University of São Paulo, Av. do Café, s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil., Oliveira CAF; Department of Food Engineering, School of Animal Science and Food Engineering, University of São Paulo, Av. Duque de Caxias - Norte, 225, CEP 13635-900, Pirassununga, SP, Brazil. |
| Abstrakt: |
In this study, hepatic biopsies from autopsy cases in São 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, β-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 β-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. |
