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Titolo:
MECHANISMS OF DNA-DAMAGE BY CHROMIUM(V) CARCINOGENS
Autore:
BOSE RN; FONKENG BS; MOGHADDAS S; STROUP D;
Indirizzi:
KENT STATE UNIV,DEPT CHEM KENT OH 44242
Titolo Testata:
Nucleic acids research
fascicolo: 7, volume: 26, anno: 1998,
pagine: 1588 - 1596
SICI:
0305-1048(1998)26:7<1588:MODBCC>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
1,10-PHENANTHROLINE COPPER-ION; CARBOXYLATO-BOUND CHROMIUM(V); APURINIC APYRIMIDINIC SITES; P-31 NMR CHARACTERIZATION; SINGLE-STRAND BREAKS; HYDROGEN-PEROXIDE; CATIONIC PORPHYRINS; NUCLEASE ACTIVITY; ELECTRON-TRANSFER; OXIDATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
61
Recensione:
Indirizzi per estratti:
Citazione:
R.N. Bose et al., "MECHANISMS OF DNA-DAMAGE BY CHROMIUM(V) CARCINOGENS", Nucleic acids research, 26(7), 1998, pp. 1588-1596

Abstract

Reactions of bis(2-ethyl-2-hydroxy-butanato)oxochromate(V) with pUC19DNA, single-stranded calf thymus DNA (ss-ctDNA), a synthetic oligonucleotide, 5'-GATCTATGGACTTACTTCAAGGCCGGGTAATGCTA-3' (35mer), deoxyguanosine and guanine were carried out in Bis-Tris buffer at pH 7.0. The plasmid DNA was only nicked, whereas the single-stranded DNA suffered extensive damage due to oxidation of the ribose moiety. The primary oxidation product was characterized as 5-methylene-2-furanone. Although all four bases (A, C, G and T) were released during the oxidation process, the concentration of guanine exceeds the other three, Orthophosphate and 3'-phosphates were also detected in this reaction, Likewise, thesynthetic oliogomer exhibits cleavage at all bases with a higher frequecncy at G sites, This increased cleavage at G sites was more apparent after treating the primary oxidation products with piperidine, whichmay indicate base oxidation as well. DNA oxidation is shown to proceed through a Cr(V)-DNA intermediate in which chromium(V) is coordinatedthrough the phosphodiester moiety. Two alternative mechanisms for DNAoxidation by oxochromate(V) are proposed to account for formation of 5-methylene-2-furanone, based on hydrogen abstraction or hydride transfer from the C1' site of the ribose followed by hydration and two successive beta-eliminations, It appears that phosphate coordination is a prerequisite for DNA oxidation, since no reactions between chromium(V)and deoxyguanosine or guanine were observed. Two other additional pathways, hydrogen abstraction from C4' and guanine base oxidation, are also discussed.

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Documento generato il 28/09/20 alle ore 12:14:58