The human immunodeficiency virus-1 Tat protein is suspected to be involved
in the neoplastic pathology arising in AIDS patients. tnt-transgenic (TT) m
ice, which constitutively express Tat in the liver, develop liver cell dysp
lasia (LCD) that may represent a preneoplastic lesion. To test if TT mice a
re predisposed to liver carcinogenesis, we treated them with diethylnitrosa
mine, a hepatotropic carcinogen. Diethylnitrosamine-treated TT mice develop
ed both preneoplastic and neoplastic lesions in the liver, They showed an e
nhancement of LCD and developed basophilic Liver cell nodules (BLCN), hepat
ocellular adenomas (HA), and hepatocellular carcinomas (HC), Both preneopla
stic (LCD and BLCN) and neoplastic (HA and HC) lesions were significantly m
ore frequent in TT than in control mice: 29.7% versus 12.7% for LCD, 57.9%
versus 23.3% for BLCN, 40.6% versus 10.0% for HA, and 50.0% versus 12.7% fo
r HC, These results indicate that Tat expression in the liver predisposes t
o both initiation of hepatocarcinogenesis and to malignant progression of l
iver tumors. This study supports a role for Tat in enhancing the effect of
endogenous and exogenous carcinogens in human immunodeficiency virus-1-infe
cted patients, thereby contributing to tumorigenesis in the course of AIDS.