Enhanced Duck Hepatitis B Virus Gene Expression Following Aflatoxin B Exposure

Abstract

Epidemiological studies have suggested synergistic interactions between chronic hepatitis B virus (HBV) infection and aflatoxin B 1 (AFB 1 ) exposure in the etiology of hepatocellular carcinoma (HCC), although the molecular mechanisms of their interactions are still not understood. The aim of this study was to use the Pekin duck model to investigate the impact of AFB 1 exposure on duck hepatitis B virus (DHBV) replication during the early stages of virus-carcinogen interactions. Six-week-old chronic DHBVcarrier or uninfected ducks were exposed to AFB 1 for 5 weeks or treated with dimethylsulfoxide (DMSO) as a control. Animals were observed for 6 to 13 weeks after AFB 1 treatment to study the influence of AFB 1 exposure on DHBV replication and liver pathologies. Histological analysis showed more marked changes in the livers of AFB 1 -treated ducks, and these were enhanced by DHBV infection. A significant increase in serum and liver DHBV DNA level was observed in AFB 1 -treated ducks as compared with DMSO-treated controls. In addition, viral RNAs, in particular the pregenomic RNA that is the template of viral replication, and intrahepatic DHBV DNA replicative intermediates, were significantly increased by AFB 1 treatment. Moreover, an overexpression and accumulation of DHBV large envelope (L) protein was observed in the hepatocytes of AFB 1 -exposed animals. The in vitro study has further confirmed an increase in intracellular viral DNA and in virus release in AFB 1 -treated primary duck hepatocytes. Taken Chronic hepatitis B virus infection (HBV) and exposure to aflatoxin B 1 (AFB 1 ) are two major risk factors that have been associated with the etiology of hepatocellular carcinoma (HCC) in humans in high-incidence areas (Africa and Southeastern Asia). 1 Moreover, several epidemiological studies in China 2,3 and in Taiwan 4 have shown that these two factors can have synergistic effects on the risk of HCC.Animal models have a pivotal role to play in understanding interactions between AFB 1 and chronic HBV infection. An earlier onset of liver tumors was observed in transgenic mice overexpressing HBV large envelope (L) protein and treated with AFB 1 as compared with the same mice not exposed to this carcinogen. 5,6 In the woodchuck model, administration of AFB 1 to woodchuck HBV-carrier animals led to a significantly earlier appearance of hepatocellular neoplasms and a higher incidence of HCC, indicating the synergistic effect of viral infection and carcinogen exposure in hepatocarcinogenesis. 7 The Pekin duck is also of interest for the study of such interactions, because it is highly sensitive to the carcinogenic effects of AFB 1 and can be infected with duck HBV (DHBV). Naturally arising liver cancers have been reported in domestic ducks in Qidong, China, where the human HCC rate is particularly high, and where exposure of humans and ducks to AFB 1 has been demonstrated. [8][9][10][11][12] Experimental administration of AFB 1 to ducks led to development of HCC with no significant differences between DHBV-infecte...

Hepatitis B infection and aflatoxin biomarker levels in Gambian children

“…These include the possibility of in utero (Wild et al 1991) and early postnatal aflatoxin exposure inducing mutations in cells that become clonally expanded by perinatal liver development and increased cell replication consequent to childhood HBV infection. Alternatively, aflatoxin exposure may modulate HBV replication (Barraud et al 1999).…”

Cytochrome P450 enzymes involved in the metabolism of aflatoxin B1 in chickens and quail

“…Although AFB 1 biotransformation in mammals is relatively well understood, studies in poultry are still needed (Savlík et al, 2007). Adverse health effects have been reported in turkeys (Quist et al, 2000;Klein et al, 2002;Rauber et al, 2007), quail (Oliveira et al, 2002), chickens (Kadian et al, 1988), and ducks (Barraud et al, 1999). However, large differences in the response of poultry species to AFB 1 have been noted (Leeson et al, 1995) and the biochemical basis for these differences has not been elucidated.…”

The role of selected cytochrome P450 enzymes on the bioactivation of aflatoxin B1 by duck liver microsomes

“…In humans, CYP1A2, CYP2A6 and CYP3A4 have been identified as the enzymes responsible for the bioactivation of AFB1 into the AFBO (Guengerich et al, 1996(Guengerich et al, , 1998Gallagher et al 1996). In poultry, adverse health effects due to aflatoxins have been reported in turkeys (Diaz et al, 2009), quails (Oliveira et al, 2002), chickens (Kadian et al, 1988) and ducks (Barraud et al, 1999). Among domestic fowl, ducks are the most sensitive species to the acute effects of aflatoxins with a median lethal dose for ducklings of 0.34 to 0.56 mg/kg body weight compared with 6.5 to 16.5 for chicks (Leeson et al, 1995).…”