title: Is there a causal association between genotoxicity and the imposex effect?
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.
authors.affiliation: Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Plymouth, Devon, United Kingdom. jhagger@plymouth.ac.uk
authors.forename: Josephine A
authors.initials: JA
authors.lastname: Hagger
authors.forename: Michael H
authors.initials: MH
authors.lastname: Depledge
authors.forename: Jörg
authors.initials: J
authors.lastname: Oehlmann
authors.forename: Susan
authors.initials: S
authors.lastname: Jobling
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Galloway
mesh_terms: D000818:Animals; D001822:Body Burden; D015331:Cohort Studies; D004249:DNA Damage / Q000187:drug effects*; D012734:Disorders of Sex Development / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D004739:England; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006066:Gonads / Q000002:abnormalities* / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D006965:Hyperplasia / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D046468:Sexual Development / Q000187:drug effects; D012908:Snails / Q000033:anatomy & histology / Q000187:drug effects; D013223:Statistics as Topic; D014220:Trialkyltin Compounds / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D004785:Environmental Pollutants; D014220:Trialkyltin Compounds; C011559:tributyltin