Related Experiment Videos
Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in lambda lacZ
V Pletsa1, M J Steenwinkel, J H van Delft
1Laboratory of Chemical Carcinogenesis, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Abstract:
Following single or multiple oral treatments of rats or lambda lacZ transgenic mice with methyl bromide, methylated DNA adducts (N7- and/or O6-methylguanine) were found at comparable levels in various tissues, including among others the glandular stomach, the forestomach and the liver. Multiple rat treatment resulted in substantial decreases in the repair enzyme O6-alkylguanine-DNA alkyltransferase which were probably due in part to direct interaction of the enzyme with methyl bromide. However, no induction of mutagenesis in the lacZ transgene could be detected in any tissue 14 days after single treatments of up to 50 mg/kg or after multiple treatments of as many as 10 daily treatments of 25 mg/kg MeBr.
Insights
Methyl bromide exposure in rats and mice formed methylated DNA adducts. However, no mutations were detected in the lacZ transgene, suggesting methyl bromide is not mutagenic under these conditions.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- Methyl bromide (MeBr) is a fumigant with known toxic properties.
- Understanding its genotoxic potential is crucial for risk assessment.
- DNA adducts are markers of exposure to genotoxic agents.
Purpose of the Study:
- To investigate the genotoxicity of methyl bromide in vivo.
- To assess the formation of DNA adducts and mutations following MeBr exposure.
- To evaluate the impact of MeBr on DNA repair mechanisms.
Main Methods:
- Oral administration of methyl bromide to rats and lambda lacZ transgenic mice.
- Quantification of methylated DNA adducts (N7- and O6-methylguanine) in various tissues.
- Assessment of mutagenesis in the lacZ transgene.
- Measurement of O6-alkylguanine-DNA alkyltransferase (MGMT) levels.
Main Results:
- Comparable levels of methylated DNA adducts were found in multiple tissues (glandular stomach, forestomach, liver) after single or multiple MeBr treatments.
- Multiple MeBr treatments led to significant decreases in the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (MGMT).
- No induction of mutagenesis in the lacZ transgene was detected 14 days after single or multiple MeBr treatments, even at high doses.
Conclusions:
- Methyl bromide exposure leads to the formation of DNA adducts in rodents.
- The observed decrease in MGMT suggests potential interaction between MeBr and the repair enzyme.
- Despite DNA adduct formation, methyl bromide did not induce detectable mutations in the lacZ transgene, indicating a lack of mutagenicity under the tested conditions.