Transgenic mice containing hepatitis B virus sequences are more susceptible to carcinogen-induced hepatocarcinogenesis.
Transgenic mice containing one copy of hepatitis B virus (HBV) genome without the core gene and expressing hepatitis B surface antigen (HBsAg) were crossed with C3H/He mice. The F1 hybrids (approximately 50% HBV positive and approximately 50% HBV negative) were treated with a single dose of diethylnitrosamine (NDEA) or p-dimethylaminoazobenzene (DAB) given at 7 days of age, or were untreated. Mice were kept under observation without further treatments until 30 weeks old and then killed. Stereological analysis of liver nodules and estimations of their size distribution demonstrated a significative enhancing effect of HBV transgene in both NDEA- and DAB-induced hepatocarcinogenesis in male mice. Hepatocellular adenomas and carcinomas were also more frequent in NDEA-treated HBV-positive than HBV-negative male mice. Female mice showed a lower tumorigenic response than males without significant differences between groups of HBV-positive and HBV-negative mice. It is proposed that the presence of the transgene enhanced carcinogen-induced hepatocarcinogenesis.
Dragani
T A
TA
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Manenti
G
G
Farza
H
H
Della Porta
G
G
Tiollais
P
P
Pourcel
C
C
D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic