Showing papers by "Betty L. Slagle published in 1996"

Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene.

Abstract: The role of the hepatitis B virus (HBV) X protein in liver tumorigenesis is unresolved. Transgenic mice harboring the X gene (nt 1376–1840 under the control of the human α-1-antitrypsin regulatory elements) (ATX mice) display only minor histopathologic alterations of the liver. To determine if ATX mice are more susceptible to the effects of hepatocarcinogens, 12- to 15-d-old male ATX and control littermate mice were injected with a single dose (2 μg/g body weight) of diethylnitrosamine (DEN). The animals were killed 6–10 mo after exposure and were analyzed for histological changes in the liver. One hundred percent of the DEN-treated ATX mice developed abnormal liver lesions. When their liver tissues were compared by stereological analysis with those of non-transgenic animals, the ATX mice had a relative twofold increase in the total number of focal lesions and a twofold increase in the incidence of hepatocellular carcinoma. Elevated levels of X protein and p53 protein were not detected in carcinogen-induced nodules or tumors. These results are consistent with a model in which the expression of the HBV X protein potentiates the induction of DEN-mediated liver disease. © 1996 Wiley-Liss, Inc.

Frequent Loss of Chromosome 8p in Hepatitis B Virus-positive Hepatocellular Carcinomas from China

Abstract: The majority of hepatocellular carcinomas (HCCs) from hepatitis B virus (HBV)-endemic areas contain integrated viral sequences To better understand the role of HBV DNA insertion in tumorigenesis, we examined the integration site of a HCC harboring a single insert Cellular DNAs flanking the viral sequences were mapped to chromosomes 17 and 8, indicating a translocation had occurred at the site of viral integration Regional mapping of chromosome 17 demonstrated that HBV had integrated in 17p12-pter, a region that harbors the p53 tumor suppressor gene Many studies have shown that chromosome 17p allele loss occurs frequently in HCCs from certain geographical areas To investigate the chromosome 8 allele status in Chinese HCCs, a panel of 37 matched normal and HCC DNAs from Qidong, China was analyzed for tumor-specific allele loss with RFLP probes from both arms of chromosome 8 Tumor-specific loss of heterozygosity was highest on the short arm with 714% (10/14) and 850% (17/20) of the informative patients missing an allele for 8p23 (YNM3) or 8p21 (NEFL), respectively Allele loss from the long arm of chromosome 8 was also observed with 300% (6/20) and 333% (7/21) of the samples informative for 8q22 (CA2) and 8q24 (MCT1282), respectively The high allele loss on 8p correlates with recent studies of other human cancers and is interpreted to indicate that a tumor suppressor gene(s) whose loss is important for carcinogenesis lies within this region These findings also support a model in which HBV insertions associated with gross chromosomal changes can identify genomic regions where alteration is important for development of some HCCs