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Carcinogenicity and Mechanisms of Persistent Organic Pollutants
Book chapter

Carcinogenicity and Mechanisms of Persistent Organic Pollutants

Gabriele Ludewig, Larry W Robertson and Howard P Glauert
Effects of Persistent and Bioactive Organic Pollutants on Human Health, pp.57-100
John Wiley & Sons, Inc
08/16/2013
DOI: 10.1002/9781118679654.ch4

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Abstract

Background: Persistent organic pollutants (POPs) are a group of halogenated organic compounds that were produced in large amounts as pesticides, industrial compounds, and production by‐products during the 1950s–1980s. Examples include the pesticides DDT and dieldrin, the polychlorinated biphenyls (PCBs) and the notorious dioxin 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD). Some of these compounds are still in use and/or produced today. However, because of their lipophilicity and resistance to destruction, they tend to biomagnify in the food chain and bioaccumulate in our bodies where they may produce a host of adverse health effects. Objectives: Most of these compounds are now classified as probable human carcinogens, some even as proven human carcinogens (TCDD and most recently PCBs as a group). This chapter will provide an insight into the stages and mechanisms of chemical carcinogenesis and the activity of these POPS in them. Discussion: The stages of chemical carcinogenesis are initiation, promotion, and progression, and each has different mechanisms and events that trigger these steps. Most POPs are believed to be promoters by changing gene transcription, acting as endocrine disruptors, producing reactive oxygen species and other mechanisms. Some members of these POPs can be regarded as initiators since they produce DNA damage either directly, after being metabolically bioactivated, or indirectly through the production of other genotoxic compounds. Some POPs may enhance progression by inducing genome instability, for example through interference with cellular proteins like telomerase or the cytoskeleton. The requirements for these stages of carcinogenesis regarding chemical structure and metabolic activation pathways are described in more detail using the large and diverse group of PCBs as an example. Conclusions: This review shows that our knowledge about the activators and mechanisms of chemical carcinogensis is incomplete. In our world of increasing exposure to mixtures of diverse chemicals a better understanding of the forces in chemical carcinogenesis is needed, to provide precautionary risk assessment and public health protective regulation.
 cancer-initiating activity environmental pollutants genotoxicity human carcinogens persistent organic pollutants (POPs)

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