Hepatic neoplasms in aflatoxin B1-treated, congenital duck hepatitis B virus-infected, and virus-free pekin ducks.
To assess the effects of the combination of persistent hepadnavirus infection and chemical carcinogen exposure, aflatoxin B1 (AFB) was administered p.o. for 60 days to congenitally duck hepatitis B virus (DHBV)-infected and virus-free Pekin ducks, starting at 3 days of age, during a 28-month study. Hepatic neoplasia occurred only in AFB-dosed ducks. Hepatocellular carcinomas or biliary carcinomas occurred in 4 of 8 DHBV-infected and 3 of 4 DHBV-free ducks, and hepatocellular adenomas developed in 2 DHBV-infected AFB-dosed ducks that survived 20 months or longer. Altered foci of hepatocytes similar to those observed in chemical carcinogen-dosed rodents, characterized by enlarged eosinophilic hepatocytes or vacuolated cytoplasm, occurred in AFB-dosed ducks. Cells in foci or hepatic neoplasms did not contain histochemically detectable gamma-glutamyltranspeptidase but were distinguished from uninvolved parenchyma by altered glycogen content. Immunohistochemical staining indicated that DHBV core antigen persisted in liver, spleen, pancreas, and, to a lesser extent, kidney of most congenitally infected ducks up to 28 months of age. Hepatic neoplasms contained only patches of hepatocytes were detectable viral antigen. Southern blot analysis of restriction endonuclease-digested neoplastic and normal liver DNA revealed high molecular weight forms of DHBV DNA consistent with integration of viral DNA into the genome of hepatic neoplasms from 3 of 4 DHBV-infected ducks but not nontumorous liver. These findings indicate that AFB is a potent hepatic carcinogen in ducks and that persistent congenital DHBV infection did not contribute significantly to the emergence of hepatic neoplasia in ducks under these conditions.
Cullen
J M
JM
North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27606.
Marion
P L
PL
Sherman
G J
GJ
Hong
X
X
Newbold
J E
JE
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000009:adverse effects*; D000686:Amyloidosis / Q000209:etiology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000032:analysis / Q000209:etiology* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004372:Ducks; D005260:Female; D015611:Hepatitis B Virus, Duck / Q000235:genetics; D006524:Hepatitis, Viral, Animal / Q000150:complications* / Q000151:congenital; D008107:Liver Diseases / Q000209:etiology; D008113:Liver Neoplasms / Q000032:analysis / Q000209:etiology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000209:etiology / Q000473:pathology; D013158:Splenic Diseases / Q000209:etiology; D005723:gamma-Glutamyltransferase / Q000032:analysis
D000348:Aflatoxins; D004273:DNA, Neoplasm; D004279:DNA, Viral; D016604:Aflatoxin B1; D005723:gamma-Glutamyltransferase