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Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
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When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
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Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
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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.

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|December 17, 2025
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Summary
This summary is machine-generated.

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.

Keywords:
biomarkerscancer preventioncancer risk assessmentmicroenvironmentpromotion

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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.