Aflatoxin B1 and/or hepatitis B virus induced tumor spectrum in a genetically engineered hepatitis B virus expression and Trp53 haploinsufficient mouse model system for hepatocarcinogenesis.
Toxicol Pathol
; 37(3): 333-42, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19258306
ABSTRACT
The authors investigated the spectrum of tumors and Trp53 mutations in genetically engineered models using the FVB/N mouse that expressed the hepatitis B virus genome and/or carried a Trp53 null and wildtype allele and/or were exposed to aflatoxin B1. Liver tumor incidence was increased when all three risk factors were present. Without aflatoxin B1 exposure, neither Trp53 haploinsufficiency nor HBV expression affected liver tumor development. Liver tumor prevalence increased with aflatoxin B1 exposure (p < .001), as thirteen of fourteen mice with liver tumors were initiated with aflatoxin B1. Liver tumors were more frequent in males (12/190) than females (2/170). Seventy-three mice developed sarcomas. Trp53 haploinsufficiency was associated with increased sarcoma incidence in males and females (p < .001). In Trp53 haploinsufficient mice, the HBV transgene increased the risk of sarcoma in males and females (p < .001). Lymphoma was significantly increased in Trp53 haploinsufficient FVB/N mice. There was no loss of heterozygosity at the wildtype Trp53 locus in twenty-five sarcomas or four hepatocellular tumors examined. No mutations were identified in the mRNA (exons 2-11) of Trp53 in six liver neoplasms or twenty-four sarcomas. In this model system, HBV expression affected only hepatocellular neoplasia in association with both aflatoxin B1 initiation and p53 haploinsufficiency.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
/
Aflatoxina B1
/
Modelos Animais de Doenças
/
Neoplasias Hepáticas Experimentais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Toxicol Pathol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos