YEARS

1991-1996

AUTHORS

Stewart Sell

TITLE

HEPATIC COCARCINOGENESIS IN TRANSGENIC MICE

ABSTRACT

The construction of transgenic mice carrying integrated hepatitis B DNA encoding the entire open reading frame for the outer membrane polypeptides of the hepatitis B virus (HBV) provides an experimental animal model in which the hypothesis that aflatoxin exposure and hepatitis B virus infection act synergistically to cause primary hepatocellular carcinoma (PHC) may be tested. PHC, while relatively rare in North America, is one of the most common cancers in some parts of the world. The marked geographic differences in the incidence of PHC have suggested that the most important risk factors for PHC are previous HBV infection and dietary exposure to aflatoxin. The present proposal will test the possible synergy between human HBV infection and dietary carcinogens by exposing transgenic mice expressing different levels of HBV to a known carcinogen (DEN) and to aflatoxin. In the first specific aim the relationship between the level of expression of HBV and carcinogen exposure will be tested in three transgenic mouse lines expressing different-levels of HBsAg polypeptide: 45-2, 45-3 and 50-4, each of which contains the HBsAg genome but which express low, intermediate and high intracellular levels of HBV polypeptide and different degrees of liver cell damage respectively. In the second specific aim, the relationship between the time of exposure and the expression will be tested using a transgenic mouse lineage in which the HBV gene is controlled by the metallothionine gene promoter. Backcrossing of transgenic males with non-transgenic females produces Fls, half of which carry the transgene and half which do not, thus providing non-transgenic littermate controls for each experimental group. Understanding the nature of the possible synergy of HBV infection and aflatoxin exposure in causing PHC could lead to ways to reduce one of the most prevalent and deadly cancers of mankind.

FUNDED PUBLICATIONS

  • Heterogeneity of the "oval-cell" response in the hamster liver during cholangiocarcinogenesis following Clonorchis sinensis infection and dimethylnitrosamine treatment.
  • articles:38bec5ae9e111021e3abdfaa4e25e76d
  • Hepatitis B injury, male gender, aflatoxin, and p53 expression each contribute to hepatocarcinogenesis in transgenic mice.
  • Characterization of a murine p53ser246 mutant equivalent to the human p53ser249 associated with hepatocellular carcinoma and aflatoxin exposure.
  • Electron microscopic identification of putative liver stem cells and intermediate hepatocytes following periportal necrosis induced in rats by allyl alcohol.
  • Control of mouse hepatocyte proliferation and ploidy by p53 and p53ser246 mutation in vivo.
  • Participation of different cell types in the restitutive response of the rat liver to periportal injury induced by allyl alcohol.
  • The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice.
  • How to use: Click on a object to move its position. Double click to open its homepage. Right click to preview its contents.

    Download the RDF metadata as:   json-ld nt turtle xml License info


    23 TRIPLES      15 PREDICATES      24 URIs      7 LITERALS

    Subject Predicate Object
    1 grants:e369003c9630f66d111d18cc49ff1da9 sg:abstract The construction of transgenic mice carrying integrated hepatitis B DNA encoding the entire open reading frame for the outer membrane polypeptides of the hepatitis B virus (HBV) provides an experimental animal model in which the hypothesis that aflatoxin exposure and hepatitis B virus infection act synergistically to cause primary hepatocellular carcinoma (PHC) may be tested. PHC, while relatively rare in North America, is one of the most common cancers in some parts of the world. The marked geographic differences in the incidence of PHC have suggested that the most important risk factors for PHC are previous HBV infection and dietary exposure to aflatoxin. The present proposal will test the possible synergy between human HBV infection and dietary carcinogens by exposing transgenic mice expressing different levels of HBV to a known carcinogen (DEN) and to aflatoxin. In the first specific aim the relationship between the level of expression of HBV and carcinogen exposure will be tested in three transgenic mouse lines expressing different-levels of HBsAg polypeptide: 45-2, 45-3 and 50-4, each of which contains the HBsAg genome but which express low, intermediate and high intracellular levels of HBV polypeptide and different degrees of liver cell damage respectively. In the second specific aim, the relationship between the time of exposure and the expression will be tested using a transgenic mouse lineage in which the HBV gene is controlled by the metallothionine gene promoter. Backcrossing of transgenic males with non-transgenic females produces Fls, half of which carry the transgene and half which do not, thus providing non-transgenic littermate controls for each experimental group. Understanding the nature of the possible synergy of HBV infection and aflatoxin exposure in causing PHC could lead to ways to reduce one of the most prevalent and deadly cancers of mankind.
    2 sg:endYear 1996
    3 sg:hasContribution contributions:73dc1f6b22b20a6d994831c21bf74f9b
    4 sg:hasFieldOfResearchCode anzsrc-for:11
    5 anzsrc-for:1103
    6 sg:hasFundedPublication articles:09690bc4a32b99803a6810371336963c
    7 articles:38bec5ae9e111021e3abdfaa4e25e76d
    8 articles:3f9b52dc5ffb90a663174a998584ca61
    9 articles:48d4b7fd69d88b3596361debf54e2578
    10 articles:794740dc9d9a89cc495dd11912eeb1a0
    11 articles:802d62566485ccd0acc5bad63dd3bbf5
    12 articles:8d1aa891ceb7f5e4b30a723c773f67f6
    13 articles:9c49de9369347fb73a1370e97d27a93b
    14 sg:hasFundingOrganization grid-institutes:grid.48336.3a
    15 sg:hasRecipientOrganization grid-institutes:grid.267308.8
    16 sg:language English
    17 sg:license http://scigraph.springernature.com/explorer/license/
    18 sg:scigraphId e369003c9630f66d111d18cc49ff1da9
    19 sg:startYear 1991
    20 sg:title HEPATIC COCARCINOGENESIS IN TRANSGENIC MICE
    21 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=2096012
    22 rdf:type sg:Grant
    23 rdfs:label Grant: HEPATIC COCARCINOGENESIS IN TRANSGENIC MICE
    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular JSON format for linked data.

    curl -H 'Accept: application/ld+json' 'http://scigraph.springernature.com/things/grants/e369003c9630f66d111d18cc49ff1da9'

    N-Triples is a line-based linked data format ideal for batch operations .

    curl -H 'Accept: application/n-triples' 'http://scigraph.springernature.com/things/grants/e369003c9630f66d111d18cc49ff1da9'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'http://scigraph.springernature.com/things/grants/e369003c9630f66d111d18cc49ff1da9'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'http://scigraph.springernature.com/things/grants/e369003c9630f66d111d18cc49ff1da9'






    Preview window. Press ESC to close (or click here)


    ...