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Identification of adenine adducts formed in reaction of calf thymus DNA with mutagenic chlorohydroxyfuranones found in drinking water.
Le Curieux, F; Munter, T; Kronberg, L.
Afiliación
  • Le Curieux F; Department of Organic Chemistry, Abo Akademi University, Turku, Finland.
Chem Res Toxicol ; 10(10): 1180-5, 1997 Oct.
Article en En | MEDLINE | ID: mdl-9348441
Calf thymus DNA was reacted with the extremely potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and the structurally related compounds 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF). The chromatograms of the HPLC analyses of the DNA hydrolysates showed peaks that represented adducted base moieties. It was possible to establish the structures of the adducts by comparing UV spectra and chromatographical properties of the DNA adducts with known adenosine and 2'-deoxyadenosine adducts. The DNA adduct produced by MX was identified as 3-(2'-deoxyribofuranosyl-N6-adenosinyl)propenal (M1A-dR). It was calculated that 1 nucleotide/10(5) nucleotides was converted to M1A-dR. The same adduct was formed also in the reaction of MX with 2'-deoxyadenosine (yield 0.01%). The M1A-dR adduct may play a role in the mutational events induced by MX in Salmonella typhimurium strain TP2428. The adducts produced in the reactions of MCA and MCF with DNA were identified as 3-(2'-deoxyribofuranosyl)-7-formylimidazo[2,1-i]purine (epsilon cA-dR) and 4-(2'-deoxyribofuranosyl-N6-adenosinyl)-3-formyl-3-butenoic acid (fbaA-dR), respectively. The yield of epsilon cA-dR was 5 adducts/ 10(6) nucleotides and of fbaA-dR 4 adducts/10(5) nucleotides. The biological significance of these adducts is unknown.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Contaminantes Químicos del Agua / Abastecimiento de Agua / Adenina / Aductos de ADN / Furanos / Mutágenos Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Chem Res Toxicol Asunto de la revista: TOXICOLOGIA Año: 1997 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Contaminantes Químicos del Agua / Abastecimiento de Agua / Adenina / Aductos de ADN / Furanos / Mutágenos Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Chem Res Toxicol Asunto de la revista: TOXICOLOGIA Año: 1997 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos