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Environmental causes of cancer: endocrine disruptors as carcinogens

Nature Reviews Endocrinology volume 6, pages 363–370 (2010)Cite this article

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Abstract

Environmental endocrine disrupting chemicals (EDCs), including pesticides and industrial chemicals, have been and are released into the environment producing deleterious effects on wildlife and humans. The effects observed in animal models after exposure during organogenesis correlate positively with an increased incidence of malformations of the male genital tract and of neoplasms and with the decreased sperm quality observed in European and US populations. Exposure to EDCs generates additional effects, such as alterations in male and female reproduction and changes in neuroendocrinology, behavior, metabolism and obesity, prostate cancer and thyroid and cardiovascular endocrinology. This Review highlights the carcinogenic properties of EDCs, with a special focus on bisphenol A. However, humans and wildlife are exposed to a mixture of EDCs that act contextually. To explain this mindboggling complexity will require the design of novel experimental approaches that integrate the effects of different doses of structurally different chemicals that act at different ages on different target tissues. The key to this complex problem lies in the adoption of mathematical modeling and computer simulations afforded by system biology approaches. Regardless, the data already amassed highlight the need for a public policy to reduce exposure to EDCs.

Key Points

  • The embryo is an open system and the environment is a co-determinant of phenotypes, such that the embryo 'reads' environmental cues as a forecast of the postnatal environment

  • Hormones act as morphogens: extemporaneous exposure to even low doses of hormonally active chemicals increases the susceptibility to various diseases, including cancer

  • Neoplasia is a tissue-based disease caused by various deleterious exposures that interfere with the reciprocal communication between cells and between cells and their surrounding extracellular matrix

  • The effects of developmental exposure to diethylstilbestrol observed in humans have been reproduced in rodent models; thus, rodents are relevant models for assessing the human toxicity of environmental endocrine disruptors

  • Endocrine disrupting chemicals act additively—their multiple and complex effects are dose-dependent and contextual; therefore, a systems biology approach should be adopted to tackle this complexity

  • Sufficient supporting data have been gathered on the deleterious effects of endocrine disrupting chemicals to warrant immediate action to decrease human and wildlife exposure to these agents

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Acknowledgements

This work was supported by grants from the Parsemus Foundation and the NIH (ES0150182, ES012301, ES08314 and ES018822). We are grateful to Cheryl Schaeberle and Michael Askenase for their excellent editorial assistance.

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  1. Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, 02111, MA, USA

    Ana M. Soto & Carlos Sonnenschein

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Soto, A., Sonnenschein, C. Environmental causes of cancer: endocrine disruptors as carcinogens. Nat Rev Endocrinol 6, 363–370 (2010). https://doi.org/10.1038/nrendo.2010.87

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