Related Experiment Videos
DNA adducts formed by the comutagens harman and norharman in various tissues of mice
K Yamashita1, H Ohgaki, K Wakabayashi
1National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
Covalent modifications of DNA in various tissues of mice with harman or norharman were analyzed by 32P-postlabeling assay. Administration of 0.1% harman to mice in their diet for 4 weeks resulted in DNA adducts in the liver and kidney. No specific DNA adduct was detected in other tissues, such as the glandular stomach, large intestine and brain. Similar treatment of mice with norharman resulted in DNA adducts in the kidney, glandular stomach and large intestine, but not in the liver or brain. These results suggests the in vivo genotoxicities of harman and norharman.
Insights
Harman and norharman cause DNA damage in mice. Harman induced DNA adducts in the liver and kidney, while norharman affected the kidney, stomach, and intestines, indicating genotoxicity.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- Harman and norharman are beta-carboline alkaloids found in various foods and beverages.
- Their potential genotoxicity and mechanisms of DNA interaction require further investigation.
Purpose of the Study:
- To investigate the in vivo genotoxicity of harman and norharman in mice.
- To identify specific tissues affected by covalent DNA modifications induced by these compounds.
Main Methods:
- Mice were fed a diet containing 0.1% harman or norharman for four weeks.
- DNA was extracted from various tissues (liver, kidney, glandular stomach, large intestine, brain).
- The 32P-postlabeling assay was employed to detect and quantify covalent DNA adducts.
Main Results:
- Harman administration resulted in significant DNA adduct formation in the liver and kidney.
- Norharman treatment led to DNA adducts in the kidney, glandular stomach, and large intestine.
- No specific DNA adducts were detected in the brain for either compound, and norharman did not adduct DNA in the liver.
Conclusions:
- Harman and norharman exhibit tissue-specific genotoxicity in vivo.
- The formation of DNA adducts suggests a potential mechanism for the carcinogenicity of these compounds.
- Further research is warranted to elucidate the precise mechanisms of DNA damage and repair for harman and norharman.