| Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. | |
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MedLine Citation:
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PMID: 11675267 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated a potential mechanism for the estrogenic properties of three chloro-s-triazine herbicides and six metabolites in vitro in several cell systems. We determined effects on human aromatase (CYP19), the enzyme that converts androgens to estrogens, in H295R (adrenocortical carcinoma), JEG-3 (placental choriocarcinoma), and MCF-7 (breast cancer) cells; we determined effects on estrogen receptor-mediated induction of vitellogenin in primary hepatocyte cultures of adult male carp (Cyprinus carpio). In addition to atrazine, simazine, and propazine, two metabolites--atrazine-desethyl and atrazine-desisopropyl--induced aromatase activity in H295R cells concentration-dependently (0.3-30 microM) and with potencies similar to those of the parent triazines. After a 24-hr exposure to 30 microM of the triazines, an apparent maximum induction of about 2- to 2.5-fold was achieved. The induction responses were confirmed by similar increases in CYP19 mRNA levels, determined by reverse-transcriptase polymerase chain reaction. In JEG-3 cells, where basal aromatase expression is about 15-fold greater than in H295R cells, the induction responses were similar but less pronounced; aromatase expression in MCF-7 cells was neither detectable nor inducible under our culture conditions. The fully dealkylated metabolite atrazine-desethyl-desisopropyl and the three hydroxylated metabolites (2-OH-atrazine-desethyl, -desisopropyl, and -desethyl-desisopropyl) did not induce aromatase activity. None of the triazine herbicides nor their metabolites induced vitellogenin production in male carp hepatocytes; nor did they antagonize the induction of vitellogenin by 100 nM (EC(50) 17beta-estradiol. These findings together with other reports indicate that the estrogenic effects associated with the triazine herbicides in vivo are not estrogen receptor-mediated, but may be explained partly by their ability to induce aromatase in vitro. |
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Authors:
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J T Sanderson; R J Letcher; M Heneweer; J P Giesy; M van den Berg |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Environmental health perspectives Volume: 109 ISSN: 0091-6765 ISO Abbreviation: Environ. Health Perspect. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-24 Completed Date: 2001-12-04 Revised Date: 2010-09-14 |
Medline Journal Info:
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Nlm Unique ID: 0330411 Medline TA: Environ Health Perspect Country: United States |
Other Details:
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Languages: eng Pagination: 1027-31 Citation Subset: IM |
Affiliation:
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Research Institute for Toxicology, Institute for Risk Assessment Sciences, University of Utrecht, 3508 TD Utrecht, The Netherlands. t.sanderson@iras.uu.nl |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aromatase / drug effects, metabolism Atrazine / adverse effects*, metabolism Carps / physiology* Enzyme Induction Hepatocytes / drug effects, physiology Herbicides / adverse effects*, metabolism Humans Male Receptors, Estrogen / drug effects, physiology Simazine / adverse effects*, metabolism Triazines / adverse effects*, metabolism Tumor Cells, Cultured Vitellogenins / biosynthesis* |
| Chemical | |
Reg. No./Substance:
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0/Herbicides; 0/Receptors, Estrogen; 0/Triazines; 0/Vitellogenins; 122-34-9/Simazine; 139-40-2/propazine; 1912-24-9/Atrazine; EC 1.14.14.1/Aromatase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
| Full Text | |
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Journal Information Journal ID (nlm-ta): Environ Health Perspect ISSN: 0091-6765 |
Article Information Download PDF  Print publication date: Month: 10 Year: 2001 Volume: 109 Issue: 10 First Page: 1027 Last Page: 1031 ID: 1242079 PubMed Id: 11675267 Publisher Item Identifier: sc271_5_1835 |
| Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. | |
| J T Sanderson | |
| R J Letcher | |
| M Heneweer | |
| J P Giesy | |
| M van den Berg | |
| Research Institute for Toxicology, Institute for Risk Assessment Sciences, University of Utrecht, 3508 TD Utrecht, The Netherlands. t.sanderson@iras.uu.nl |
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