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A correlative approach for the identification of antimutagens that demonstrate chemopreventive activity
L A Shamon1, C Chen, R G Mehta
1Program for Collorative Research in the Pharmaceutical Sciences, University of Illinois at Chicago 60612.
Abstract:
Seventy natural and synthetic compounds were tested for potential to inhibit mutation induced by 7,12-dimethylbenz(a)anthracene (DMBA) in Salmonella typhimurium strain TM677. Results were compared with their ability to inhibit DMBA-induced preneoplastic lesions in a mouse mammary gland organ culture system. The response mediated by fifty-five of the test compounds was either positive or negative in both test systems, indicating that the combined use of these assays should aid in the discovery of antimutagenic agents that have cancer chemopreventive potential.
Insights
Researchers screened 70 compounds for antimutagenic and cancer chemopreventive potential. A high correlation between mutation inhibition and preneoplastic lesion prevention suggests these assays can identify effective agents.
Area of Science:
- Chemoprevention
- Mutagenesis
- Toxicology
Background:
- 7,12-dimethylbenz(a)anthracene (DMBA) is a known mutagen and carcinogen.
- Assessing antimutagenic and chemopreventive properties is crucial for cancer research.
- Salmonella typhimurium strain TM677 and mouse mammary gland organ cultures are established models for such assessments.
Purpose of the Study:
- To evaluate the potential of 70 natural and synthetic compounds to inhibit DMBA-induced mutations.
- To compare the efficacy of these compounds in preventing DMBA-induced preneoplastic lesions in mouse mammary glands.
- To determine the correlation between the two test systems for identifying cancer chemopreventive agents.
Main Methods:
- Utilized Salmonella typhimurium strain TM677 for mutagenicity assays.
- Employed mouse mammary gland organ culture system to assess preneoplastic lesion inhibition.
- Tested 70 compounds for their inhibitory effects in both systems against DMBA exposure.
Main Results:
- Fifty-five compounds showed consistent responses (positive or negative) in both the mutagenicity and chemoprevention assays.
- A significant overlap in compound activity was observed between the two distinct biological systems.
- The results demonstrate a strong correlation between antimutagenic activity and cancer chemopreventive potential.
Conclusions:
- The combined use of Salmonella mutagenicity assays and mouse mammary gland organ cultures is effective for discovering antimutagenic agents.
- This dual-assay approach can accelerate the identification of compounds with cancer chemopreventive properties.
- The findings support the development of novel strategies for cancer prevention through natural and synthetic compounds.