Carcinogen definition
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Understanding Carcinogens: Definition and Mechanisms
Definition of Carcinogens
A carcinogen is any substance, radionuclide, or radiation that is directly involved in causing cancer. This can include both natural and synthetic substances, as well as various forms of radiation such as gamma rays and alpha particles 34. Carcinogens are not immediately toxic, meaning their harmful effects can manifest gradually over time 3.
Genotoxic and Non-Genotoxic Carcinogens
Carcinogens can be classified based on their mode of action into genotoxic and non-genotoxic categories. Genotoxic carcinogens directly damage the DNA, leading to mutations that can result in cancer. Non-genotoxic carcinogens, on the other hand, do not directly damage DNA but can cause cancer through other mechanisms such as chronic inflammation or hormonal imbalances 125.
Genotoxic Carcinogens
Genotoxic carcinogens interact with DNA, causing mutations that can lead to cancer. These mutations can activate proto-oncogenes or inactivate tumor suppressor genes, both of which are critical in the regulation of cell growth and division 68. Examples of genotoxic carcinogens include certain chemicals and forms of radiation that cause direct DNA damage 57.
Non-Genotoxic Carcinogens
Non-genotoxic carcinogens do not directly cause DNA damage but can lead to cancer through other mechanisms. These include inducing oxidative stress, causing chronic inflammation, or altering cell proliferation and death 127. For instance, substances like asbestos and certain dioxins fall into this category 3.
Dose-Response Relationship
The risk posed by a carcinogen is often related to the dose and duration of exposure. High doses of a carcinogen are generally associated with a higher risk of cancer, while lower doses pose a lower risk 12. For genotoxic carcinogens, there is typically no safe threshold dose, meaning any exposure could potentially lead to cancer. In contrast, non-genotoxic carcinogens may have a threshold dose below which they do not pose a significant cancer risk 12.
Mechanisms of Carcinogenesis
Carcinogenesis is a multistep process involving genetic and epigenetic changes. These changes can provide cells with a growth advantage, leading to clonal expansion and tumor formation. Key mechanisms include the activation of proto-oncogenes, inactivation of tumor suppressor genes, and alterations in DNA repair processes 68.
Key Characteristics of Carcinogens
The International Agency for Research on Cancer (IARC) has identified ten key characteristics commonly exhibited by human carcinogens. These include the ability to act as an electrophile, be genotoxic, alter DNA repair, induce oxidative stress, and cause chronic inflammation, among others 7. These characteristics help in systematically evaluating the mechanistic data to support conclusions regarding human hazard from exposure to carcinogens.
Conclusion
Carcinogens are agents that can cause cancer through various mechanisms, including direct DNA damage and other non-genotoxic pathways. Understanding the dose-response relationship and the specific mechanisms of action is crucial for assessing the risk posed by different carcinogens. This knowledge is essential for developing effective strategies to minimize exposure and reduce cancer risk.
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What is the meaning of ‘A compound is carcinogenic’?
The term 'carcinogenic' should be based on scientific analysis of the compound's genotoxic or non-genotoxic properties, dose-response behavior, and mode-of-action, rather than a general public perception of danger.
Exposure to Carcinogens and its effects in the Formation of Cancer
Exposure to carcinogens can lead to the formation of cancer by damaging the genome or disrupting cellular metabolic processes.
Carcinogenic agents and cancer treatment
Carcinogens are substances that directly cause cancer, or can cause cancer through their radiation effects.
Carcinogenesis and Carcinogens that are also Genotoxic
Carcinogenicity experiments face challenges in defining genotoxicity and interpreting results, particularly with genotoxic carcinogens.
Chemical and physical carcinogenesis: advances and perspectives for the 1990s.
Carcinogen-induced genetic and epigenetic damage in susceptible cells leads to carcinogenesis, with both exogenous and endogenous mechanisms contributing to the process.
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Systematic Review
Very Rigorous JournalHighly CitedCellular and molecular mechanisms of multistep carcinogenesis: relevance to carcinogen risk assessment.
Chemical carcinogens influence carcinogenesis through mutational activation of protooncogenes and/or inactivation of tumor suppressor genes, with their carcinogenic risk based on their combined effects on multiple genetic and epigenetic processes.
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