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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
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Rethinking the microenvironment's role in chemical-induced malignancy
William H Bisson1, Richard A Currie2, Emilia L Lim3
1Integrative Toxicology and Cancer Prevention, Research Triangle Park, NC 27560, United States.
Summary
Cancer initiation involves complex interactions between carcinogen exposures and the tissue microenvironment, shifting focus from DNA mutations to environmental signals promoting tumor growth. Understanding this microenvironment is key for cancer risk assessment and prevention.
Area of Science:
- Toxicology
- Cancer Biology
- Environmental Health
Background:
- Cancer origins are shifting from a focus on DNA mutations to the role of the tissue microenvironment.
- Carcinogen exposures significantly alter the microenvironment, influencing tumorigenesis.
- The microenvironment's role in cancer development is complex and tissue-specific.
Purpose of the Study:
- To review the evidence linking chemical-induced microenvironmental changes to cancer development.
- To discuss phenotypic alterations associated with carcinogen-driven microenvironmental changes.
- To highlight the importance of the microenvironment in cancer hazard evaluation and prevention.
Main Methods:
- Literature review and expert consensus from a Society of Toxicology symposium.
- Analysis of experimental evidence on chemical exposures and microenvironmental alterations.
- Discussion of assays and biomarkers for assessing chemical-microenvironment-cancer links.
Main Results:
- Carcinogen exposures induce microenvironmental changes like inflammation, neo-angiogenesis, and immune tolerance.
- These changes promote tumor development through mechanisms like clonal expansion and cellular plasticity.
- Evidence links chemical-driven microenvironmental alterations to various solid and liquid tumors.
Conclusions:
- The tissue microenvironment plays a critical role in chemical carcinogenesis.
- Understanding microenvironmental impacts is essential for accurate cancer hazard evaluation.
- This knowledge can inform next-generation risk assessment, prevention strategies, and patient care.
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