Brevetoxin forms covalent DNA adducts in rat lung following intratracheal exposure.
BACKGROUND: Human exposure to brevetoxins produced by the red tide organism, Karenia brevis, is an increasing public health concern. Using in vitro exposure of rat liver cells to brevetoxin B (PbTx-2), the primary toxin product of K. brevis, we previously showed that it formed C(27,28)-epoxy breveto...
| Publicado en: | Environmental Health Perspectives Vol. 116; no. 7; pp. 930 - 937 |
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| Autores principales: | , |
| Formato: | research Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Jul2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105654681&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105654681 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Jul2008 vid: 116 iid: 7 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 105654681 105654681 2009966730 10.1289/ehp.11068 NLM18629316 105654681 ppf: 930 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Brevetoxin forms covalent DNA adducts in rat lung following intratracheal exposure. aug: au: Radwan FFY Ramsdell JS affil: Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, National Oceanic and Atmospheric Administration/National Ocean Service, Charleston, South Carolina, USA sug: subj: DNA Metabolism Heterocyclic Compounds Lung Drug Effects Marine Toxins Protozoa Animals DNA Lung Metabolism Lung Rats Animal Studies ab: BACKGROUND: Human exposure to brevetoxins produced by the red tide organism, Karenia brevis, is an increasing public health concern. Using in vitro exposure of rat liver cells to brevetoxin B (PbTx-2), the primary toxin product of K. brevis, we previously showed that it formed C(27,28)-epoxy brevetoxin metabolites capable of covalently binding to nucleic acids, a common initiation step for carcinogenesis. OBJECTIVE: This study was undertaken to evaluate nucleic acid adduction in lung following in vitro and in vivo brevetoxin exposures. METHODS: To clarify reactions of brevetoxin epoxide with DNA, we analyzed reaction products of PbTx-6 (a C(27,28) epoxide metabolite of brevetoxin B) with nucleosides. We also analyzed adducts from nucleic acid hydrolysates of isolated rat lung cells treated with PbTx-2 or PbTx-6 in vitro and lung tissue from rats after intratracheal exposure to PbTx-2 or PbTx-6 at 45 microg toxin/kg body weight. RESULTS: Our results indicate that PbTx-2 forms DNA adducts with cytidine after treatment of isolated lung cells, and forms DNA adducts with adenosine and guanosine after intratracheal exposure. CONCLUSIONS: These results are consistent with metabolic activation of highly reactive brevetoxin intermediates that bind to nucleic acid. These findings provide a basis for monitoring exposure and assessing the hazard associated with depurination of brevetoxin-nucleotide adducts in lung tissue. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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