Linked Life Data

7634431

Source:http://linkedlifedata.com/resource/pubmed/id/7634431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1995-9-14
pubmed:abstractText
Both male DBA/2J and C3H/HeJ mice are highly susceptible to hepatocarcinogenesis induced by experimental treatment with N,N-diethylnitrosamine (DEN) relative to male C57BL/6J mice. While C3H/HeJ mice carry multiple sensitivity loci, designated Hcs (hepatocarcinogen sensitivity), our previous study indicated that the susceptibility of DBA/2J mice results from the combined effects of multiple sensitivity loci and two major resistance loci, Hcr-1 and -2 (hepatocarcinogen resistance). We proposed that BXD-15 recombinant inbred mice, which are extremely resistant to DEN-induced hepatocarcinogenesis, may carry the Hcr loci from the parental DBA/2J mice, but few, if any, of the multiple sensitivity loci. Conversely, the extremely sensitive BXD-11 recombinant inbred mice may carry most of the multiple sensitivity loci of the DBA/2J parents, but neither of the major resistance loci. In order to confirm our genetic model for hepatocarcinogenesis in DBA/2J mice and to evaluate the phenotypic effects of the Hcr loci on the Hcs loci of C3H/HeJ mice, we characterized hepatocarcinogen sensitivities of F1 mice generated from the crosses involving BXD-11, BXD-15, C3H/HeJ and C57BL/6J strains. When male mice were initiated with DEN at 12 days of age and liver tumors were enumerated at 32 weeks of age, (BXD-15 x BXD-11)F1 mice had one sixth the number of liver tumors observed in (C57BL/6J x BXD-11)F1 mice, consistent with our previous conclusion that DBA/2J mice possess hepatocarcinogen resistance genes in spite of their high susceptibility to DEN. Significantly, (C57BL/6J x C3H/HeJ)F1 mice also had a 2.3-fold greater number of liver tumors and 5.5-fold higher total volume of initiated lesions per liver as compared with (BXD-15 x C3H/HeJ)F1 mice, indicating that the hepatocarcinogen resistance genes inherited by BXD-15 mice are capable of suppressing the Hcs phenotype. Thus the Hcr loci may influence a wide variety of hepatocarcinogen sensitivity loci and be able to act as general resistance loci for chemical hepatocarcinogenesis. Stereological analysis of initiated hepatocellular lesions with glucose 6-phosphatase deficiency revealed that the resistance genes largely influence the promotion stage of hepatocarcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1993-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
The Hcr (hepatocarcinogen resistance) loci of DBA/2J mice partially suppress phenotypic expression of the Hcs (hepatocarcinogen sensitivity) loci of C3H/HeJ mice.
pubmed:affiliation
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.