| Is There a Causal Association between Genotoxicity and the Imposex Effect? Josephine A. Hagger,1 Michael H. Depledge,1,2 Jörg Oehlmann,3 Susan Jobling,4 and Tamara S. Galloway1 1Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Plymouth, Devon, United Kingdom; 2Environment Agency of England and Wales, Almondsbury, Bristol, United Kingdom; 3Department of Ecology and Evolution - Ecotoxicology, University of Frankfurt, Frankfurt, Germany; 4Brunel University, Uxbridge, Middlesex, United Kingdom Abstract
There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT) -induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways. Key words: ecotoxicology, endocrine disruption, genotoxicity, imposex, micronucleus, Nucella lapillus, tributyltin. Environ Health Perspect 114(suppl 1) :20-26 (2006) . doi:10.1289/ehp.8048 available via http://dx.doi.org/ [Online 21 October 2005]
This article is part of the monograph "The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife." Address correspondence to J.A. Hagger, Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK. Telephone: 01751 232797. Fax: 01752 232970. E-mail: jhagger@plymouth.ac.uk The genotoxic research was supported by a Leverhulme Trust grant (F/00 568/D) . The authors declare they have no competing financial interests. Received 31 January 2005 ; accepted 11 July 2005.
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