Detection and quantification of adducts formed upon interaction of diamminedichloroplatinum (II) with DNA, by anion-exchange chromatography after enzymatic degradation

Fichtinger-Schepman, Anne Marie J.; Lohman, P.H.M.; Reedijk, Jan

doi:10.1093/nar/10.17.5345

Cited by 152 publications

(73 citation statements)

References 10 publications

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“…The N7-atoms of guanine (G) and to a lesser extent adenine (A) are the preferred reaction sites (3). The major lesions induced by treatment of isolated mammalian DNA with cis-DDP have been characterized as 1,2 intrastrand cross-links between adjacent bases in GG and AG sequences, which correspond to 60-65% and 20-25% of the total amounts of platinum adducts, respectively (4,5,6,7). Rarer lesions are 1,3 intrastrand cross-links between G residues separated by one base residue in GNG sequences (5-6% of platinum adducts), interstrand cross-links between G residues in opposing strands of the DNA helix (1-2%), and platinum-DNA monoadducts (2-3%) (6,7,8).…”

Section: Introductionmentioning

confidence: 99%

Repair synthesis by human cell extracts in DNA damaged bycis- andtrans-diamminedichloroplatinum(II)

Hansson¹,

Wood

1989

Nucl Acids Res

109

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DNA damage was induced in closed circular plasmid DNA by treatment with cis-or transdiamminedichloroplatinum(l). These plasmids were used as substrates in reactions to give quantitative measurements of DNA repair synthesis mediated by cell free extracts from human lymphoid cell lines. Adducts induced by both drugs stimulated repair synthesis in a dose dependent manner by an ATP-requiring process. Measurements by an isopycnic gradient sedimentation method gave an upper limit for the average patch sizes in this in vitro system of around 140 nucleotides. It was estimated that up to 3% of the drug adducts induce the synthesis of a repair patch. The repair synthesis is due to repair of a small fraction of frequent drug adducts, rather than extensive repair of a rare subclass of lesions. Nonspecific DNA synthesis in undamaged plasmids, caused by exonucleolytic degradation and resynthesis, was reduced by repeated purification of intact circular forms. An extract made from cells belonging to xeroderma pigmentosum complementation group A was deficient in repair synthesis in response to the presence of cis-or trans-diamminedichloroplatinum(ll) adducts in DNA.

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Section: Introductionmentioning

confidence: 99%

Repair synthesis by human cell extracts in DNA damaged bycis- andtrans-diamminedichloroplatinum(II)

Hansson¹,

Wood

1989

Nucl Acids Res

109

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“…Cisplatin and its analog CBDCA are potent anticancer agents that covalently bind to DNA bases, thereby disrupting normal cellular function (8)(9)(10)(11)(12)(13). Cisplatin-induced DNA modifications are well characterized and include DNA interstrand cross-links (9), DNA-protein cross-links (9), DNA monoadducts (10,12), and bidentate-intrastrand DNA adducts (10)(11)(12).…”

mentioning

confidence: 99%

“…Cisplatin-induced DNA modifications are well characterized and include DNA interstrand cross-links (9), DNA-protein cross-links (9), DNA monoadducts (10,12), and bidentate-intrastrand DNA adducts (10)(11)(12). A major portion of the total cisplatin bound to DNA in eukaryotic cells (11,12) is in the form of the bidentateintrastrand adducts of diammineplatinum covalently linked to the N7 positions of adenosine and/or guanosine.…”

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confidence: 99%

Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy.

Reed¹,

Ozols²,

Tarone³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

191

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Fifty-five ovarian cancer patients receiving platinum drug-based chemotherapy have been studied prospectively to determine the extent of formation of the bidentate intrastrand adducts of diammineplatinum covalently attached to the N7 positions of adenosine and/or guanosine in leukocyte DNA. Data for clinical response, obtained from medical records, were then correlated with the adduct values. Patients were treated with platinum-based single-agent or combination chemotherapy containing cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum on approved experimental protocols. Adduct measurements were performed by ELISA, and disease response to therapy was assessed by standard oncologic criteria. This study comprises a total of 101 blood samples obtained after intravenous cisdiamminedichloroplatinum (II) or diamminecyclobutanedicarboxylatoplatinum infusion from 55 individuals, and in each case the highest (or "peak") adduct level for each patient was chosen for statistical analysis. Values for median adduct levels in patients grouped by complete response, partial response, and no response were 212, 193, and 62 amol of adduct per ,ug of DNA, respectively. Analysis of these data by Jonckheere's test (an extension of the Mann-Whitney test) shows that higher levels of adduct formation correlates with disease response with a two-sided P value of 0.030. Of eight patients on single-agent therapy whose buffy-coat samples did not have measurable adduct levels, none responded to therapy. Analysis of these data using the exact test for trend shows that the formation of adduct at a level of 160 amol/,ug of DNA or greater correlates with disease response with a two-sided P value of 0.032. Thus in ovarian cancer patients, the formation of the intrastrand diammineplatinum adducts in leukocyte DNA is associated with favorable disease response to cisdiamminedichloroplatinum (II) or diamminecyclobutanedicarboxylatoplatinum chemotherapy.

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“…The overwhelmingly preferred binding sites are the GpG and ApG sequences [17][18][19][20][21] and there are indications that sequences with more than two guanine bases are favoured [22,23]. Binding to isolated guanine bases is inherently preferred over binding to isolated adenine bases [24] but outer-sphere complex formation prior to binding also has the potential to influence the final product distribution.…”

Section: Introductionmentioning

confidence: 99%

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

et al. 1998

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Detection and quantification of adducts formed upon interaction of diamminedichloroplatinum (II) with DNA, by anion-exchange chromatography after enzymatic degradation

Cited by 152 publications

References 10 publications

Repair synthesis by human cell extracts in DNA damaged bycis- andtrans-diamminedichloroplatinum(II)

Repair synthesis by human cell extracts in DNA damaged bycis- andtrans-diamminedichloroplatinum(II)

Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy.

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

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