PMID: 7513828May 1, 1994Paper

Formation and persistence of DNA adducts in pouch skin fibroblasts and liver tissue of rats exposed in vivo to the monofunctional alkylating agents N-methyl-N-nitrosourea or N-ethyl-N-nitrosourea

Mutation Research
Jacob G JansenAlbert A van Zeeland

Abstract

Base substitutions and frameshifts induced by genotoxic agents are considered to result mainly from incomplete repair and incorrect replication of modified nucleotides in DNA. In this study, induction and persistence of O6-alkyl- and 7-alkylguanine adducts were determined by reverse phase HPLC and electrochemical detection in DNA of pouch skin fibroblasts and liver tissue of rats exposed in vivo to the monofunctional alkylating agents N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU). Although an exposure dependent increase in the level of adducts was found for both chemicals, a much lower frequency of both O6-alkylguanine and 7-alkylguanine was detected after ENU treatment than after MNU treatment, indicating that MNU is much more reactive with DNA than ENU. The persistence of O6-alkyl- and 7-alkylguanine was studied for up to 48 h at exposure levels of 60 mg/kg for MNU and 100 mg/kg for ENU. A time-dependent decline in the levels of both adducts was observed, but w6-alkylguanine was more rapidly lost than 7-alkylguanine in both pouch skin fibroblasts and liver. Furthermore, DNA adducts were faster lost from liver than from pouch skin fibroblasts. The loss of O6-alkylguanine adducts is probably mediated by the actio...Continue Reading

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Citations

Aug 17, 1996·Mutation Research·B J Sanderson, A J Shield
May 1, 1995·Toxicology Letters·A A van ZeelandH Vrieling
Jun 6, 2000·Mutation Research·J EngelbergsM F Rajewsky
Sep 28, 1998·Mutation Research·S A Kyrtopoulos
Dec 31, 1997·Mutation Research·A AidooD A Casciano
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S W WijnhovenH Vrieling
Jan 1, 2000·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·V OreffoP B Farmer
Apr 4, 2020·Journal of Food Biochemistry·Wafaa H MohamedAdel S Mahmoud

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