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Endogenous and background DNA adducts by methylating and 2-hydroxyethylating agents
1Center for Nutrition and Toxicology, Department of Biosciences, Karolinska Institute, NOVUM, S-141 57 Huddinge, Sweden.
Mutation Research
|March 5, 1999
Summary
This study measured 7-methylguanine (7-MG) and 7-hydroxyethylguanine (7-HEG) DNA adducts in humans and rats. Smokers showed higher 7-MG levels, indicating increased DNA damage from alkylating agents.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Background:
- 7-alkylguanine DNA adducts are biomarkers of exposure to alkylating agents.
- Assessing these adducts helps evaluate DNA damage and human exposure levels.
- Background levels vary between tissues and populations.
Purpose of the Study:
- To determine background levels of 7-methylguanine (7-MG) and 7-hydroxyethylguanine (7-HEG) DNA adducts in human and rat tissues.
- To compare adduct levels in smokers versus non-smokers.
- To investigate 7-HEG adduct accumulation in rats exposed to ethene.
Main Methods:
- Thin-layer chromatography (TLC) combined with high-performance liquid chromatography (HPLC) was used for adduct detection.
- Human tissue samples (WBC, lung, bronchus) were analyzed from smokers and non-smokers.
- Rat tissues were analyzed for background adducts and after ethene exposure.
Main Results:
- Non-smokers had background 7-alkylguanine adducts of 2.9 (WBC) and 4.0 (lung) adducts/10^7 nucleotides.
- Smokers with lung cancer showed significantly higher 7-MG levels in lung and bronchus tissues compared to WBC.
- Ethene exposure in rats led to similar 7-HEG accumulation across liver, lymphocytes, and kidney.
Conclusions:
- Elevated 7-MG adducts in smokers suggest increased DNA damage from alkylating agents.
- Background 7-MG levels are higher than 7-HEG levels in rats.
- 7-HEG adducts accumulate in rat tissues upon ethene exposure, indicating its genotoxic potential.