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WA2 Chemical and Biological Analysis of Endocrine Disrupting Compounds
() Endocrine toxicity: Is there an association between genotoxicity and endocrine disruption in wildlife?
Hagger, J1, Jobling, S2, Oehlmann, J3, Depledge, M4, Galloway, T1, 1 University of Plymouth, Plymouth, Devon, UK2 Brunel University, Uxbridge, UK3 Frankfurt University, Frankfurt, Germany4 Environment Agency, Bristol, UK
ABSTRACT- It is well known that many xenobiotics in the environment are capable of disrupting the endocrine system of both wildlife and humans. In humans, exposure to endocrine disrupting chemicals (EDCs) has been hypothesised to play a role in the reported decrease in sperm counts in some areas, and in the increase in the incidence of breast and prostate cancers. It is well established that some hormones can act as cellular proliferators and could therefore serve as cancer promoters or epigenetic carcinogens. New evidence indicates that hormonal metabolites may directly induce damage to genetic material, raising the possibility that pollutant-induced endocrine disruption might not occur in isolation, but might be just one of a suite of toxicological effects. The dogwhelk, Nucella lapillus, which exhibits recognisable alterations in their endocrine system was tested for evidence of genetic damage. A field study of N. lapillus exposed to the antifouling agent tributyltin (TBT), indicating a correlation (R = 0.9356; p=0.0001) between DNA damage (micronucleus assay) and incidence of imposex (masculinisation of females). In addition, 18,697 dogwhelks were sampled from over 100 locations between 1988 and 2004 and examined for the presence of abnormalities of the reproductive tract and (at three additional sites) for evidence of genetic damage. The results revealed a widespread incidence of imposex and a low incidence of neoplastic growths primarily on the vas deferens and penis of the males and imposex females. The incidence of this phenomenon increased with imposex stages of females and attained an incidence of 31.8% in the most masculinized individuals. Overall, there was a strong correlation between the vas deferens sequence index (VDSI) in the imposexed females and the prevalence of proliferations on the genital organs (r=0.793; p<0.0005) and a concommittant association between the TBT body burden and the prevalence of the proliferations in these animals(r=0.788; p<0.0005). The possible mechanisms of action of these effects, either through direct damage to DNA, induction of apoptosis, or modulation of signal transduction pathways that normally regulate cell cycle repair checkpoint functions, is discussed in relation to pollutant-induced disruption of endocrine processes in different organisms.
Key words: Genotoxicity, Endocrine disruption, Nucella lapillus , Neoplasia
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