Induction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats following treatment with 2-acetylaminofluorene.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95262
Title:
Induction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats following treatment with 2-acetylaminofluorene.
Authors:
Chinnasamy, Nachimuthu; Rafferty, Joseph A; Margison, Geoffrey P; O'Connor, Peter J; Elder, Rhoderick H
Abstract:
Molecular and immunohistological techniques have been used to study the induction in rat liver of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase), following an acute dose (60 mg/kg) of the hepatocarcinogen, 2-acetylaminofluorene (2-AAF). An increase in ATase activity was specific to the liver, with a five- to six-fold induction being observed 72 hr after administration of 2-AAF. A similar temporal increase of both activity and ATase protein (detected by immunoblotting) was observed up to 1 week following treatment, but after 2 weeks the activity had returned to control levels. Although maximal induction of hepatic ATase mRNA was observed as early as 24 hr, the levels remained elevated at least 1 week after 2-AAF treatment. Using a rabbit antiserum raised against purified recombinant rat ATase, ATase-specific staining was observed in the nuclei of both nonhepatocytes and hepatocytes in control liver sections. There was, however, a significant differential staining of hepatocytes across the liver lobule, with ATase staining being most intense in the periportal region. In the livers of 2-AAF-treated rats, an increased intensity of staining was observed in hepatocytes throughout the liver lobule, whereas the nonparenchymal cells showed much less, or no, increase in staining. The increased expression of ATase in hepatocytes and its differential distribution across the lobule were confirmed by image analysis. Thus, ATase induction in response to 2-AAF treatment was an hepatocyte-specific response and not confined to any particular region of the liver lobule.
Affiliation:
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Citation:
Induction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats following treatment with 2-acetylaminofluorene. 1997, 16 (4):493-500 DNA Cell Biol.
Journal:
DNA and Cell Biology
Issue Date:
Apr-1997
URI:
http://hdl.handle.net/10541/95262
PubMed ID:
9150437
Type:
Article
Language:
en
ISSN:
1044-5498
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorChinnasamy, Nachimuthuen
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorO'Connor, Peter Jen
dc.contributor.authorElder, Rhoderick Hen
dc.date.accessioned2010-03-30T14:18:48Z-
dc.date.available2010-03-30T14:18:48Z-
dc.date.issued1997-04-
dc.identifier.citationInduction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats following treatment with 2-acetylaminofluorene. 1997, 16 (4):493-500 DNA Cell Biol.en
dc.identifier.issn1044-5498-
dc.identifier.pmid9150437-
dc.identifier.urihttp://hdl.handle.net/10541/95262-
dc.description.abstractMolecular and immunohistological techniques have been used to study the induction in rat liver of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase), following an acute dose (60 mg/kg) of the hepatocarcinogen, 2-acetylaminofluorene (2-AAF). An increase in ATase activity was specific to the liver, with a five- to six-fold induction being observed 72 hr after administration of 2-AAF. A similar temporal increase of both activity and ATase protein (detected by immunoblotting) was observed up to 1 week following treatment, but after 2 weeks the activity had returned to control levels. Although maximal induction of hepatic ATase mRNA was observed as early as 24 hr, the levels remained elevated at least 1 week after 2-AAF treatment. Using a rabbit antiserum raised against purified recombinant rat ATase, ATase-specific staining was observed in the nuclei of both nonhepatocytes and hepatocytes in control liver sections. There was, however, a significant differential staining of hepatocytes across the liver lobule, with ATase staining being most intense in the periportal region. In the livers of 2-AAF-treated rats, an increased intensity of staining was observed in hepatocytes throughout the liver lobule, whereas the nonparenchymal cells showed much less, or no, increase in staining. The increased expression of ATase in hepatocytes and its differential distribution across the lobule were confirmed by image analysis. Thus, ATase induction in response to 2-AAF treatment was an hepatocyte-specific response and not confined to any particular region of the liver lobule.en
dc.language.isoenen
dc.subject.mesh2-Acetylaminofluorene-
dc.subject.meshAnimals-
dc.subject.meshDNA Repair-
dc.subject.meshEnzyme Induction-
dc.subject.meshImage Processing, Computer-Assisted-
dc.subject.meshImmunohistochemistry-
dc.subject.meshLiver-
dc.subject.meshMale-
dc.subject.meshMethyltransferases-
dc.subject.meshMutagens-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshRNA, Messenger-
dc.subject.meshRats-
dc.titleInduction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats following treatment with 2-acetylaminofluorene.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.en
dc.identifier.journalDNA and Cell Biologyen
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.