Journal Article

Cell proliferation and global methylation status changes in mouse liver after phenobarbital and/or choline-devoid, methionine-deficient diet administration

Jennifer L. Counts, Juan I. Sarmiento, Margaret L. Harbison, John C. Downing, R.Michael McClain and Jay I. Goodman

in Carcinogenesis

Volume 17, issue 6, pages 1251-1257
Published in print June 1996 | ISSN: 0143-3334
Published online June 1996 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/17.6.1251
Cell proliferation and global methylation status changes in mouse
                    liver after phenobarbital and/or choline-devoid, methionine-deficient
                    diet administration

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Our laboratory is testing the hypothesis that hypomethylation of DNA [a decreased content of 5-methylcytosine (5MeC) compared with cytosine] facilitates aberrant oncogene expression involved in tumorigenesis, using a model system of mouse strains with differing susceptibilities to liver tumorigenesis. The B6C3F1 (C57BL/6 × C3H/He) mouse serves as the relatively susceptible strain and C57BL/ 6 serves as the relatively resistant strain. Phenobarbital (PB)and/or administration of a choline-devoid, methionine-deficient diet (CMD) were employed as non-genotoxic hepatocarcinogens. We have examined hepatocyte and non-hepatocyte proliferation in conjunction with an assessment of global methylation changes in liver DNA of B6C3F1 and C57BL/6 mice following these promoter treatments. Bromodeoxyuridine incorporation into DNA, used to measure cell proliferation indirectly, was visualized by immunohistochemistry and quantified by aMacintosh-based image analysis system. Increased hepatocyte proliferation was demonstrated following all three treatments.This increase was larger in C57BL/6 (the relatively resistant strain) as compared with B6C3F1. In contrast, global hypomethylation was evident to a larger extent in the B6C3F1 mouse, as compared with C57BL/6. PB led to hypomethylation (>20% decrease as compared with controls) at weeks 1, 2 and 4 in B6C3F1, but not in C57BL/6 at the same time points. CMD diet administration led to hypomethylation in both strains. At week 1, 21 and 9% decreasesin global methylation status were observed in B6C3F1 and C57BL/ 6 respectively. Evaluation of these data suggests that the heightened sensitivity of the B6C3F1 mouse compared with the C57BL/6 is due, in part, to a decreased capacity for, or fidelity of, maintaining normal methylation status. The relatively resistant strain is better able to maintain the normal methylation status of DNA in the face of a higher level of cell proliferation.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.