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Environmental causes of cancer: endocrine disruptors as carcinogens

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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References

  1. Wingspread consensus statement in Chemically Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection (eds Colborn, T. & Clement, C.) 1–8 (Princeton Scientific Publishing, Princeton, 1992).

  2. Colborn, T., vom Saal, F. S. & Soto, A. M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ. Health Perspect. 101, 378–384 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sharpe, R. M. & Skakkebaek, N. E. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 341, 1392–1395 (1993).

    Article  CAS  PubMed  Google Scholar 

  4. Davis, D. L. et al. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ. Health Perspect. 101, 372–377 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Markey, C. M., Rubin, B. S., Soto, A. M. & Sonnenschein, C. Endocrine disruptors: from Wingspread to environmental developmental biology. J. Steroid Biochem. Mol. Biol. 83, 235–244 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. vom Saal, F. S. et al. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod. Toxicol. 24, 131–138 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Crain, D. A. et al. Cellular bioavailability of natural hormones and environmental contaminants as a function of serum and cytosolic binding factors. Toxicol. Ind. Health 14, 261–273 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Diamanti-Kandarakis, E. et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 30, 293–342 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kavlock, R. J. et al. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U. S. EPA-sponsored workshop. Environ. Health Perspect. 104 (Suppl. 4), 715–740 (1996).

    PubMed  PubMed Central  Google Scholar 

  10. Huggins, C. Endocrine-induced regression of cancers. Science 156, 1050–1054 (1967).

    Article  CAS  PubMed  Google Scholar 

  11. Mori, T., Bern, H. A., Mills, K. T. & Young, P. N. Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice. J. Natl Cancer Inst. 57, 1057–1061 (1976).

    Article  CAS  PubMed  Google Scholar 

  12. Lacassagne, A. Endocrine factors concerned in the genesis of experimental mammary carcinoma. J. Endocrinol. 13, ix–xviii (1955).

    CAS  PubMed  Google Scholar 

  13. Huggins, C. Endocrine-induced regression of cancers. Cancer Res. 27, 1925–1930 (1967).

    CAS  PubMed  Google Scholar 

  14. Gilbert, S. F., Opitz, J. M. & Raff, R. A. Resynthesizing evolutionary and developmental biology. Dev. Biol. 173, 357–372 (1996).

    Article  CAS  PubMed  Google Scholar 

  15. Griffiths, P. E. & Gray, R. D. in Cycles of Contingency: Developmental Systems and Evolution (eds Oyama, S., Griffiths, P. E. & Gray, R. D.) 195–218 (MIT Press, Cambridge, 2000).

    Google Scholar 

  16. Sonnenschein, C. & Soto, A. M. The Society of Cells: Cancer and Control of Cell Proliferation (Springer Verlag, New York, 1999).

    Google Scholar 

  17. Baker, S. G. & Kramer, B. S. Paradoxes in carcinogenesis: new opportunities for research directions. BMC Cancer 7, 151 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Phillips, R. B. Adaptive evolution or genetic drift? Does genome complexity produce organismal complexity? Heredity 93, 122–123 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Moss, L. What Genes Can't Do (MIT Press, Cambridge, MA, 2003).

    Google Scholar 

  20. Hull, D. The Philosophy of Biological Science (Prentice Hall, Englewood Clifts, NJ, 1974).

    Google Scholar 

  21. Gilbert, S. F. & Sarkar, S. Embracing complexity: organicism for the 21st century. Dev. Dyn. 219, 1–9 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Noble, D. The Music of Life: Biology beyond the Genome (Oxford University Press, Oxford, 2006).

    Google Scholar 

  23. Ritter, W. E. & Bailey, E. W. The organismal conception: its place in science and its bearing on philosophy. Univ. Calif. Pub. Zool. 31, 307–358 (1928).

    Google Scholar 

  24. Gilbert, S. F. & Epel, D. Ecological Developmental Biology (Sinauer Associates, Sunderland, MA, 2009).

    Google Scholar 

  25. Gilbert, S. F. Mechanisms for the environmental regulation of gene expression: ecological aspects of animal development. J. Biosci. 30, 65–74 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Barker, D. J., Eriksson, J. G., Forsén, T. & Osmond, C. Fetal origins of adult disease: strength of effects and biological basis. Int. J. Epidemiol. 31, 1235–1239 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Soto, A. M., Sonnenschein, C. & Miquel, P. A. On physicalism and downward causation in developmental and cancer biology. Acta Biotheor. 56, 257–274 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Weinberg, R. A. One Renegade Cell: How Cancer Begins (Basic Books, New York, 1998).

    Google Scholar 

  29. Ho, S.-M., Tang, W. Y., Belmonte de Frausto, J. & Prins, G. S. Developmental exposure to estradiol and bisphenol a increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res. 66, 5624–5632 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Keri, R. A. et al. An evaluation of evidence for the carcinogenic activity of bisphenol A. Reprod. Toxicol. 24, 240–252 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Soto, A. M. & Sonnenschein, C. The somatic mutation theory of cancer: growing problems with the paradigm? Bioessays 26, 1097–1107 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Cooper, M. Regenerative pathologies: stem cells, teratomas and theories of cancer. Medicine Studies 1, 55–66 (2009).

    Article  Google Scholar 

  33. Baker, S. G. et al. Plausibility of stromal initiation of epithelial cancers without a mutation in the epithelium: a computer simulation of morphostats. BMC Cancer 9, 89–99 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sonnenschein, C. & Soto, A. M. Theories of carcinogenesis: an emerging perspective. Semin. Cancer Biol. 18, 372–377 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zarbl, H., Sukumar, S., Arthur, A. V., Martin-Zanca, D. & Barbacid, M. Direct mutagenesis of Ha-ras-1 oncogenes by n-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature 315, 382–385 (1985).

    Article  CAS  PubMed  Google Scholar 

  36. Maffini, M. V., Soto, A. M., Calabro, J. M., Ucci, A. A. & Sonnenschein, C. The stroma as a crucial target in rat mammary gland carcinogenesis. J. Cell Sci. 117, 1495–1502 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Barcellos-Hoff, M. H. & Ravani, S. A. Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res. 60, 1254–1260 (2000).

    CAS  PubMed  Google Scholar 

  38. Maffini, M. V., Calabro, J. M., Soto, A. M. & Sonnenschein, C. Stromal regulation of neoplastic development: Age-dependent normalization of neoplastic mammary cells by mammary stroma. Am. J. Pathol. 67, 1405–1410 (2005).

    Article  Google Scholar 

  39. Hendrix, M. J. et al. Reprogramming metastatic tumour cells with embryonic microenvironments. Nat. Rev. Cancer 7, 246–255 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Coleman, W., Wennerberg, A. E., Smith, G. J. & Grisham, J. W. Regulation of the differentiation of diploid and aneuploid rat liver epithelial (stemlike) cells by the liver microenvironment. Am. J. Pathol. 142, 1373–1382 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Mintz, B. & Ilmensee, K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl Acad. Sci. USA 72, 3585–3589 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. vom Saal, F. S. & Bronson, F. H. Sexual characteristics of adult female mice are correlated with their blood testosterone levels during prenatal development. Science 208, 597–599 (1980).

    Article  CAS  PubMed  Google Scholar 

  43. Vandenberg, L. N. et al. Exposure to the xenoestrogen bisphenol-A alters development of the fetal mammary gland. Endocrinology 148, 116–127 (2007).

    Article  CAS  PubMed  Google Scholar 

  44. vom Saal, F. S., Grant, W. M., McMullen, C. W. & Laves, K. S. High fetal estrogen concentrations: correlation with increased adult sexual activity and decreased aggression in male mice. Science 220, 1306–1309 (1983).

    Article  CAS  PubMed  Google Scholar 

  45. Markey, C. M., Michaelson, C. L., Veson, E. C., Sonnenschein, C. & Soto, A. M. The rodent uterotrophic assay: response to Ashby and Newbold et al. Environ. Health Perspect. 109, A569–A570 (2001).

    Article  PubMed Central  Google Scholar 

  46. Markey, C. M., Wadia, P. R., Rubin, B. S., Sonnenschein, C. & Soto, A. M. Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract. Biol. Reprod. 72, 1344–1351 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Mittendorf, R. Teratogen update: carcinogenesis and teratogenesis associated with exposure to diethylstilbestrol (DES) in utero. Teratology 51, 435–445 (1995).

    Article  CAS  PubMed  Google Scholar 

  48. Kurita, T., Mills, A. & Cunha, G. R. Roles of p63 in the diethylstilbestrol-induced cervicovaginal adenosis. Development 131, 1639–1649 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Newbold, R. R., Moore, A. B. & Dixon, D. Characterization of uterine leiomyomas in CD-1 mice following developmental exposure to diethylstilbestrol (DES). Toxicol. Pathol. 30, 611–616 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Burroughs, K. D., Fuchs-Young, R., Davis, R. & Walker, C. L. Altered hormonal responsiveness of proliferation and apoptosis during myometrial maturation and the development of uterine leiomyomas in the rat. Biol. Reprod. 63, 1322–1330 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Miller, C., Degenhardt, K. & Sassoon, D. A. Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis. Nat. Genet. 20, 228–230 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Baird, D. D. & Newbold, R. Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development. Reprod. Toxicol. 20, 81–84 (2005).

    Article  CAS  PubMed  Google Scholar 

  53. Rothschild, T. C., Boylan, E. S., Calhoon, R. E. & Vonderhaar, B. K. Transplacental effects of diethylstilbestrol on mammary development and tumorigenesis in female ACI rats. Cancer Res. 47, 4508–4516 (1987).

    CAS  PubMed  Google Scholar 

  54. Boylan, E. S. & Calhoon, R. E. Mammary tumorigenesis in the rat following prenatal exposure to diethylstilbestrol and postnatal treatment with 7, 12-dimethylbenz[a]anthracene. J. Toxicol. Environ. Health 5, 1059–1071 (1979).

    Article  CAS  PubMed  Google Scholar 

  55. Palmer, J. R. et al. Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiol. Biomarkers Prev. 15, 1509–1514 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Trichopoulos, D. Is breast cancer initiated in utero? Epidemiology 1, 95–96 (1990).

    Article  CAS  PubMed  Google Scholar 

  57. Braun, M. M., Ahlbom, A., Floderus, B., Brinton, L. A. & Hoover, R. N. Effect of twinship on incidence of cancer of the testis, breast, and other sites (Sweden). Cancer Causes Control 6, 519–524 (1995).

    Article  CAS  PubMed  Google Scholar 

  58. Potischman, N. & Troisi, R. In-utero and early life exposures in relation to risk of breast cancer. Cancer Causes Control 10, 561–573 (1999).

    Article  CAS  PubMed  Google Scholar 

  59. Halakivi-Clarke, L., Cho, E., Onojafe, I., Liao, D. J. & Clarke, R. Maternal exposure to tamoxifen during pregnancy increases carcinogen-induced mammary tumorigenesis among female rat offspring. Clin. Cancer Res. 6, 305–308 (2000).

    CAS  PubMed  Google Scholar 

  60. Calafat, A. M., Ye, X., Wong, L. Y., Reidy, J. A. & Needham, L. L. Exposure of the U. S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ. Health Perspect. 116, 39–44 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Schönfelder, G. et al. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ. Health Perspect. 110, A703–A707 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Sun, Y. et al. Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection. Biomed. Chromatogr. 18, 501–507 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Wong, K. O., Leo, L. W. & Seah, H. L. Dietary exposure assessment of infants to bisphenol A from the use of polycarbonate baby milk bottles. Food Addit. Contam. 22, 280–288 (2005).

    Article  CAS  Google Scholar 

  64. Durando, M. et al. Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ. Health Perspect. 115, 80–86 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Murray, T. J., Maffini, M. V., Ucci, A. A., Sonnenschein, C. & Soto, A. M. Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod. Toxicol. 23, 383–390 (2007).

    Article  CAS  PubMed  Google Scholar 

  66. Jenkins, S. et al. Oral exposure to bisphenol A increases dimethylbenzanthracene-induced mammary cancer in rats. Environ. Health Perspect. 117, 910–915 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Muñoz-de-Toro, M. M. et al. Perinatal exposure to bisphenol A alters peripubertal mammary gland development in mice. Endocrinology 146, 4138–4147 (2005).

    Article  PubMed  CAS  Google Scholar 

  68. Vandenberg, L. N. et al. Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod. Toxicol. 26, 210–219 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hatch, E. E. et al. Cancer risk in women exposed to diethylstilbestrol in utero. JAMA 280, 630–634 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. Couse, J. F. et al. Accelerated onset of uterine tumors in transgenic mice with aberrant expression of the estrogen receptor after neonatal exposure to diethylstilbestrol. Mol. Carcinog. 19, 236–242 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Steenland, K., Bertazzi, P., Baccarelli, A. & Kogevinas, M. Dioxin revisited: developments since the 1997 IARC classification of dioxin as a human carcinogen. Environ. Health Perspect. 112, 1265–1268 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kogevinas, M. Human health effects of dioxins: cancer, reproductive and endocrine system effects. Hum. Reprod. Update 7, 331–339 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Buchanan, D. L., Sato, T., Peterson, R. E. & Cooke, P. S. Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse uterus: critical role of the aryl hydrocarbon receptor in stromal tissue. Toxicol. Sci. 57, 302–311 (2000).

    Article  CAS  PubMed  Google Scholar 

  74. Fenton, S. E., Hamm, J. T., Birnbaum, L. & Youngblood, G. L. Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Sci. 67, 63–74 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Brown, N. M., Manzolillo, P. A., Zhang, J. X., Wang, J. & Lamartiniere, C. A. Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis 19, 1623–1629 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Høyer, A. P., Grandjean, P., Jørgensen, T., Brock, J. W. & Hartvig, H. B. Organochlorine exposure and risk of breast cancer. Lancet 352, 1816–1820 (1998).

    Article  PubMed  Google Scholar 

  77. Cohn, B. A., Wolff, M. S., Cirillo, P. M. & Sholtz, R. I. DDT and breast cancer in young women: new data on the significance of age at exposure. Environ. Health Perspect. 115, 1406–1414 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Ibarluzea, J. M. et al. Breast cancer risk in the combined effect of environmental estrogens. Cancer Causes Control 15, 591–600 (2004).

    Article  Google Scholar 

  79. Skakkebaek, N. E., Rajpert- De Meyts, E. & Main, K. M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 16, 972–978 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Hardell, L., Bavel, B., Lindstrom, G., Eriksson, M. & Carlberg, M. In utero exposure to persistent organic pollutants in relation to testicular cancer risk. Int. J. Androl. 29, 228–234 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Timms, B. G. et al. Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. Proc. Natl Acad. Sci. USA 102, 7014–7019 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Timms, B. G., Peterson, R. E. & vom Saal, F. S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses. Toxicol. Sci. 67, 264–274 (2002).

    Article  CAS  PubMed  Google Scholar 

  83. Bosland, M. C. et al. Multistage prostate carcinogenesis: the role of hormones. Princess Takamatsu Symp. 22, 109–123 (1991).

    CAS  PubMed  Google Scholar 

  84. Huang, L., Pu, Y., Alam, S., Birch, L. & Prins, G. S. Estrogenic regulation of signaling pathways and homeobox genes during rat prostate development. J. Androl. 25, 330–337 (2004).

    Article  CAS  PubMed  Google Scholar 

  85. Prins, G. S., Birch, L., Tang, W.-Y. & Ho, S.-M. Developmental estrogen exposures predispose to prostate carcinogenesis with aging. Reprod. Toxicol. 23, 374–382 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Crain, D. A. et al. Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing. Fertil. Steril. 90, 911–940 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Howdeshell, K. L., Hotchkiss, A. K., Thayer, K. A., Vandenbergh, J. G. & vom Saal, F. S. Exposure to bisphenol A advances puberty. Nature 401, 763–764 (1999).

    Article  CAS  PubMed  Google Scholar 

  88. Newbold, R. R., Padilla-Banks, E., Jefferson, W. N. & Heindel, J. J. Effects of endocrine disruptors on obesity. Int. J. Androl. 31, 201–208 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Rubin, B. S., Murray, M. K., Damassa, D. A., King, J. C. & Soto, A. M. Perinatal exposure to low doses of bisphenol-A affects body weight, patterns of estrous cyclicity and plasma LH levels. Environ. Health Perspect. 109, 675–680 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Nunez, A. A., Kannan, K., Giesy, J. P., Fang, J. & Clemens, L. G. Effects of bisphenol A on energy balance and accumulation in brown adipose tissue in rats. Chemosphere 42, 917–922 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Alonso-Magdalena, P., Morimoto, S., Ripoll, C., Fuentes, E. & Nadal, A. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ. Health Perspect. 114, 106–112 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Kortenkamp, A. Breast cancer, oestrogens and environmental pollutants: a re-evaluation from a mixture perspective. Int. J. Androl. 29, 193–198 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Moriyama, K. et al. Thyroid hormone action is disrupted by bisphenol A as an antagonist. J. Clin. Endocrinol. Metab. 87, 5185–5190 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Noble, D. From the Hodgkin-Huxley axon to the virtual heart. J. Physiol. 580, 15–22 (2007).

    Article  CAS  PubMed  Google Scholar 

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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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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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