Oxidative damage of DNA by chromium(V) complexes: relative importance of base versus sugar oxidation
Biochemistry & Molecular Biology; in-vitro; nucleic-acids; abstraction; aqueous-solution; carcinogen chromium(vi); hydrogen; molecular-oxygen; radical formation; redox potentials; singlet oxygen; strand breaks
Chromium(V)-mediated oxidative damage of deoxyribonucleic acids was investigated at neutral pH in aqueous solution by utilizing bis(2-ethyl-2-hydroxybutanato)oxochromate(V) (I) and bis(hydroxyethyl)amino-tris(hydroxymethyl)methane)oxochromate(V) (II). Single-stranded and double-stranded (ds) calf thymus and human placenta DNA, as well as two oligomers, 5'-GATCTAGTAGGAGGACAAATAGTGTPTG-3' and 5'-GATCCAAGCAAACACTATTTGTCCTCCTACTA-3', were reacted with the chromium(V) complexes. Most products were separated and characterized by chromatographic and spectroscopic methods, Polyacrylamide gel electrophoresis experiments reveal more damage at G sites in comparison to other bases. Three primary oxidation products, 5-methylene-2-furanone (5-MF), furfural and 8-oxo-2'-deoxyguanosine, were characterized, A minor product, which appears to be thymine propenal, was also observed. The dsDNA produces more furfural than furanone, The formation of these two products resulted from hydrogen abstraction dr hydride transfer from C1' and C5' positions of the ribose to the oxo-chromium(V) center. Since no enhancements of these products (except propenal) were observed in the presence of oxygen, mechanisms pertaining to the participation of activated oxygen species may be ruled out. The oxidation of the G base is most likely associated with an oxygen atom transfer from the oxo-metallates to the double bond between C8 and N7 of the purine ring. The formation of the propenal may be associated with an oxygen-activated species, since a marginal enhancement of this product was observed in the presence of oxygen, The formation of furfural in higher abundance over 5-MF for dsDNA was attributed to the ease of hydrogen abstraction (or hydride transfer) from the C5' compared to C1' position of the ribose within a Cr(V)-DNA intermediate in which the metal center is bound to the phosphate diester moiety.
Bose R N; Moghaddas S; Mazzer P A; Dudones L P; Joudah L; Stroup D
Nucleic Acids Research
1999
1999-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1093/nar/27.10.2219" target="_blank" rel="noreferrer noopener">10.1093/nar/27.10.2219</a>
Potentiation Of The Antiviral Activity Of Poly R(a-u) By Xanthene Dyes
Cell Biology; flow-cytometry; inducers; inhibition; interferon; living cells; Localization; Mitochondria; nucleic-acids; protein-synthesis; rhodamine-123
Jamison J M; Krabill K; Hatwalkar A; Jamison E; Tsai C C
Cell Biology International Reports
1990
1990-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0309-1651(90)90015-q" target="_blank" rel="noreferrer noopener">10.1016/0309-1651(90)90015-q</a>
Ultrastructural nucleolar alterations induced by an ametantrone/polyr(A-U) complex
actinomycin-d; Cell Biology; cells; fibrillar centers; human interferon; invitro antiviral activity; mitoxantrone; novatrone; nucleic-acids; Oncology; photodynamic therapy; poly r(a-u); rna-synthesis
In the present study we examined the ultrastructural modifications as well as the precise distribution of DNA and RNA in RT4 cell nucleoli following a 3-h exposure to nontoxic or toxic doses of ametantrone (AMT), poly(adenylate-uridylate) (polyr(A-U), or an AMT/polyr(A-U) combination, While distribution of nucleic acids within the various nucleolar components is not modified following all treatments, the nucleoli exhibit several ultrastructural changes: redistribution of the nucleolar components, decrease in the number of fibrillar centers, and increase in the size of the fibrillar centers, The relative frequencies of the test agents to induce the apparition of nucleoli of compact type are AMT/polyr(A-U) > AMT approximate to polyr(A-U) > sham-treated, while the abilities of the test agents to induce the nucleolar segregation are AMT/polyr(A-U) approximate to AMT > polyr(A-U) > sham-treated cells, These ultrastructural changes are characteristic of drugs that intercalate into DNA and inhibit rDNA transcription as well as rRNA processing and release of nascent preribosomes from the nucleolus. (C) 1997 Academic Press.
Thiry M; Jamison J M; Gilloteaux J; Summers J L; Goessens G
Experimental Cell Research
1997
1997-10
Journal Article
<a href="http://doi.org/10.1006/excr.1997.3743" target="_blank" rel="noreferrer noopener">10.1006/excr.1997.3743</a>