pubmed-article:2972290 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C0013227 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C0012854 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C0054858 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C0205460 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C0733689 | lld:lifeskim |
pubmed-article:2972290 | lifeskim:mentions | umls-concept:C1706536 | lld:lifeskim |
pubmed-article:2972290 | pubmed:issue | 19 | lld:pubmed |
pubmed-article:2972290 | pubmed:dateCreated | 1988-11-9 | lld:pubmed |
pubmed-article:2972290 | pubmed:abstractText | We have studied the effects of the recently reported two new metabolites of the antitumor agent VP-16-213, the ortho-dihydroxy derivative or catechol and the ortho-quinone, on the biological activity of single-stranded and double-stranded phi X174 DNA, the binding of the metabolites to calf thymus DNA and the conversion of the catechol into the ortho-quinone. Evidence was obtained for the oxidation of the catechol into the ortho-quinone and for the fact that the ortho-quinone is the metabolite of VP-16-213 responsible for its binding to rat liver microsomal proteins. The catechol and ortho-quinone of VP-16-213 were found to bind 7-9 times more strongly to calf thymus DNA than VP-16-213 itself. In contrast to the parent compound VP-16-213, the catechol as well as the ortho-quinone inactivated both single-stranded (ss) and double-stranded (RF) biologically active phi X174 DNA. The mean T37-values for inactivation of ss and RF phi X174 DNA by 2.2 x 10(-4)M catechol at 37 degrees and pH 7.4 were 96 and 640 min, respectively. Reduction of the ortho-quinone by NADPH cytochrome P-450 reductase resulted in formation of the catechol. The system ortho-quinone/NADPH cytochrome P-450 reductase inactivated ss phi X174 DNA with a mean T37-value of 454 min, and this inactivation was inhibited by DMSO. The mean T37-value for inactivation of ss phi X174 DNA by 1.8 x 10(-4) M ortho-quinone at 37 degrees and pH 4.0 was 24 min. The chemical stability of the ortho-quinone and the extent of inactivation of ss phi X174 DNA by the ortho-quinone were both pH-dependent: at higher pH the ortho-quinone was less stable and gave less inactivation of DNA. The aqueous decomposition product(s) of the ortho-quinone formed at pH 7.4 inactivated ss phi X174 DNA with a mean T37-value of 175 min. The rate of inactivation of RF phi X174 DNA by the ortho-quinone at pH 4.0 was twice as low as the rate of inactivation of ss phi X174 DNA: T37 = 49 min. When using excision repair deficient E. coli mutants (uvrA- or uvrC-), a higher inactivation of RF phi X174 DNA was found: T37 = 29 min for uvrA- E. coli, indicating that a part of the DNA damage introduced by the incubation with ortho-quinone is removed by excision repair.(ABSTRACT TRUNCATED AT 400 WORDS) | lld:pubmed |
pubmed-article:2972290 | pubmed:language | eng | lld:pubmed |
pubmed-article:2972290 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:2972290 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:2972290 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:2972290 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:2972290 | pubmed:month | Oct | lld:pubmed |
pubmed-article:2972290 | pubmed:issn | 0006-2952 | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:van MaanenJ... | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:de VriesJJ | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:PinedoH MHM | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:LafleurM VMV | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:PILZHH | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:RetèlJJ | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:de RuiterCC | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:van den... | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:KootstraP RPR | lld:pubmed |
pubmed-article:2972290 | pubmed:author | pubmed-author:PappieDD | lld:pubmed |
pubmed-article:2972290 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:2972290 | pubmed:day | 1 | lld:pubmed |
pubmed-article:2972290 | pubmed:volume | 37 | lld:pubmed |
pubmed-article:2972290 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:2972290 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:2972290 | pubmed:pagination | 3579-89 | lld:pubmed |
pubmed-article:2972290 | pubmed:dateRevised | 2003-11-14 | lld:pubmed |
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pubmed-article:2972290 | pubmed:year | 1988 | lld:pubmed |
pubmed-article:2972290 | pubmed:articleTitle | Effects of the ortho-quinone and catechol of the antitumor drug VP-16-213 on the biological activity of single-stranded and double-stranded phi X174 DNA. | lld:pubmed |
pubmed-article:2972290 | pubmed:affiliation | Department of Oncology, Free University Hospital, Amsterdam, The Netherlands. | lld:pubmed |
pubmed-article:2972290 | pubmed:publicationType | Journal Article | lld:pubmed |
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