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Novel coumarins as potential anticarcinogenic agents.
R V Nair1, E P Fisher, S H Safe
1University of Texas, M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville 78957.
Carcinogenesis
|January 1, 1991
Summary
Novel coumarin derivatives show promise in preventing polycyclic aromatic hydrocarbon-mediated skin cancer. One derivative effectively inhibited tumor initiation by blocking DNA adduct formation in mice.
Area of Science:
- Biochemistry
- Toxicology
- Carcinogenesis
Background:
- Polycyclic aromatic hydrocarbons (PAHs) are known carcinogens.
- Novel coumarin derivatives based on PAHs were synthesized.
- Understanding their anticarcinogenic potential is crucial.
Purpose of the Study:
- To evaluate the anticarcinogenic properties of novel coumarin derivatives.
- To assess their interaction with the aryl hydrocarbon receptor (AhR).
- To investigate their effect on PAH-DNA adduct formation and tumor initiation.
Main Methods:
- Assessing competitive binding to rat cytosolic Ah-receptor.
- Measuring mouse epidermal aryl hydrocarbon hydroxylase (AHH) activity post-topical application.
- Quantifying hydrocarbon-DNA adducts in vivo.
- Evaluating inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumors in SENCAR mice.
Main Results:
- Compounds showed good correlation between Ah-receptor binding and AHH induction.
- 8-methyl-9H-10-oxabenzo[a]pyren-9-one exhibited highest Ah-receptor affinity and AHH induction.
- This coumarin derivative significantly inhibited DMBA-DNA adduct formation.
- It also significantly inhibited DMBA-induced skin tumor initiation (69-76% inhibition).
Conclusions:
- The studied coumarin derivatives show potential as inhibitors of PAH-mediated tumor initiation.
- 8-methyl-9H-10-oxabenzo[a]pyren-9-one is a promising candidate for further development.
- These compounds may offer a strategy for preventing skin cancer caused by PAHs.