Short Communication Enhancement of Chemical Hepatocarcinogenesis by the HIV-1 tat Gene

The human immunodeficiency virus-1 Tat protein is suspected to be involved in the neoplastic pathology arising in AIDS patients. tat-transgenic (TT) mice, which constitutively express Tat in the liver, develop liver cell dysplasia (LCD) that may represent a preneoplastic lesion. To test if TT mice are predisposed to liver carcinogenesis, we treated them with diethylnitrosamine, a hepatotropic carcinogen. Diethylnitrosamine-treated TT mice developed both preneoplastic and neoplastic lesions in the liver. They showed an enhancement of LCD and developed basophilic liver cell nodules (BLCN), hepatocellular adenomas (HA), and hepatocellular carcinomas (HC). Both preneoplastic (LCD and BLCN) and neoplastic (HA and HC) lesions were significantly more 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% for HC. These results indicate that Tat expression in the liver predisposes to both initiation of hepatocarcinogenesis and to malignant progression of liver tumors. This study supports a role for Tat in enhancing the effect of endogenous and exogenous carcinogens in human immunodeficiency virus-1-infected patients, thereby contributing to tumorigenesis in the course of AIDS. (Am J Pathol 2000, 157:1081‐1089)