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PMID: 7317030 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Effect of partial hepatectomy on removal of O6-methylguanine from alkylated DNA by rat liver extracts.

The Biochemical journal ·Vol. 197 ·No. 1 ·1981-07-01 ·Pages 195-201

Pegg AE, Perry W, Bennett RA

Abstract

1. The activity of an enzyme catalysing the loss of O6-methylguanine from methylated DNA was increasing during liver regeneration after partial hepatectomy. Activity was increased 3-fold by 24h and was maximal (6-fold increase) over the period 48-72h after operation. 2. This activity could also be induced by chronic treatment with dimethylnitrosamine, but the maximal response amounted to a 2-3-fold change (with the greater effect in male rats) after 4-6 weeks of exposure to daily doses of 2 mg of dimethylnitrosamine/kg. 3. Neither partial hepatectomy nor treatment with dimethylnitrosamine increased the activities of two other enzymes repairing alkylated DNA, DNA (7-methylguanine-)glycosylase and DNA (3-methyladenine-)glycosylase. 4. These results therefore indicate that there is a selective induction of the O6-methylguanine removal system during hepatocyte proliferation. Since this product is known to lead to mutations and its persistence in DNA throughout cell replication has been implicated in tumour initiation, this induction may play a role in resistance to carcinogenesis by alkylating agents.

MeSH Terms
Alkylation Animals DNA Repair Dimethylnitrosamine/pharmacology Female Guanine/analogs & derivatives,metabolism Hepatectomy Liver/drug effects,metabolism Liver Regeneration Male Methyltransferases/metabolism O(6)-Methylguanine-DNA Methyltransferase Proteins/metabolism Rats Time Factors
Chemicals
Proteins Guanine O-(6)-methylguanine Methyltransferases O(6)-Methylguanine-DNA Methyltransferase Dimethylnitrosamine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pegg A E
Perry W
Bennett R A
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37 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj1970195
Published
1981-07-01
Pages
195-201
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1163070
Subset
IM
Grants
NCI NIH HHS · 1P30 CA 18450 · United States
NCI NIH HHS · CA 18137 · United States
External Links
PubMed source DOI: 10.1042/bj1970195 PMC Full Text View journal details
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