title: Transcriptional responses in Japanese medaka (Oryzias latipes) exposed to binary mixtures of an estrogen and anti-estrogens.
abstract: Determining ecotoxicological risks of exposure to mixtures of endocrine disrupting chemicals (EDCs) remains a daunting challenge in environmental toxicology. Recently, some studies have illustrated that transcriptional profiling of genes offers the potential to identify the chemical causation of effects that are induced by exposure to complex mixtures. In the present study, the transcriptional responses of a set of genes involved in the hypothalamic-pituitary-gonadal (HPG, or HPG[L]-liver) axis of Japanese medaka (Oryzias latipes) were systematically examined after treatment with a combination of an estrogen (17α-ethinylestradiol [EE2], 20 ng/L) and two model anti-estrogens, the aromatase inhibitor (AI) letrozole (LET) and the selective estrogen-receptor modulator (SERM) tamoxifen (TAM), at three concentrations (30, 100 and 300 μg/L) for 72 h. The data presented demonstrate that although gene transcription analyses increase our mechanistic understanding of the modes of action (MOAs) of EDCs, the characteristic of most genes altered by a certain single chemical exposure may not be useful for diagnostic chemical causation in a mixture exposure situation. For example, the induction of one vitellogenin gene (VTG1) transcription caused by EE2 in male fish was effectively blocked after exposure to a combination of EE2 and LET but not EE2 and TAM. Moreover, the responses in gene transcription to coexposure were elicited partially in a nonmonotonic concentration-dependent manner. Therefore, the application of transcriptional profiling of genes for screening complex environmental samples should be further evaluated until biomarker gene responses are robust and sensitive enough to properly assess the complex interactions.
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, PR China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Sun
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Shao
authors.forename: Xinhua
authors.initials: X
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Chi
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.forename: Weihong
authors.initials: W
authors.lastname: Ye
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D045424:Complex Mixtures / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects; D020847:Estrogen Receptor Modulators / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000633:toxicity; D009990:Oryzias / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D012737:Sex Factors; D013629:Tamoxifen / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects*; D014230:Triazoles / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D045424:Complex Mixtures; D052244:Endocrine Disruptors; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D014874:Water Pollutants, Chemical; D013629:Tamoxifen; D004997:Ethinyl Estradiol; D000077289:Letrozole