Linked Life Data

19323581

Source:http://linkedlifedata.com/resource/pubmed/id/19323581

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-18
pubmed:abstractText
Platinum chemotherapeutic agents have been widely used in the treatment of cancer. Cisplatin was the first of the platinum-based chemotherapeutic agents and therefore has been extensively studied as an antitumor agent since the late 1960s. Because this agent forms several DNA adducts, a highly sensitive and specific quantitative assay is needed to correlate the molecular dose of individual adducts with the effects of treatment. An ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for quantification of 1,2 guanine-guanine intrastrand cisplatin adducts [CP-d(GpG)], using (15)N(10) CP-d(GpG) as an internal standard, was developed. The internal standard was characterized by MS/MS, and its concentration was validated by inductively coupled plasma mass spectrometry. Samples containing CP-d(GpG) in DNA were purified by enzyme hydrolysis, centrifugal filtration, and HPLC with fraction collection prior to quantification by UPLC-MS/MS in the selective reaction monitoring mode [m/z 412.5-->248.1 for CP-d(GpG); m/z 417.5-->253.1 for [(15)N(10)] CP-d(GpG)]. The recovery of standards was >90%, and quantification was unaffected by increasing concentrations of calf thymus DNA. This method utilizes 25 mug of DNA per injection. The limit of quantification was 3 fmol or 3.7 adducts per 10(8) nucleotides, which approaches the sensitivity of the (32)P postlabeling method for this adduct. These data suggested that this method is suitable for in vitro and in vivo assessment of CP-d(GpG) adducts formed by cisplatin and carboplatin. Subsequently, the method was applied to studies using ovarian carcinoma cell lines and C57/BL6 mice to illustrate that this method is capable of quantifying CP-d(GpG) adducts using biologically relevant systems and doses. The development of biomarkers to determine tissue-specific molecular dosimetry during treatment will lead to a more complete understanding of both therapeutic and adverse effects of cisplatin and carboplatin. This will support the refinement of therapeutic regimes and appropriate individualized treatment protocols.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-10463593, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-10542106, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-14998487, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-15351281, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-15374956, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-16571898, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-1703029, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-17636892, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-17728458, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-17932658, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-1855275, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-18716833, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-18950280, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-1999494, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-2458857, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-2720647, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-3110781, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-3317449, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-3539322, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-3741840, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-5449435, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-6225458, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-6891601, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-7599137, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-7753620, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-7937961, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-8075509, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-8318875, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-8319613, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-8756462, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-8765478, http://linkedlifedata.com/resource/pubmed/commentcorrection/19323581-9541678
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-5010
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
905-12
pubmed:dateRevised
2011-5-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Development of an ultraperformance liquid chromatography/mass spectrometry method to quantify cisplatin 1,2 intrastrand guanine-guanine adducts.
pubmed:affiliation
Curriculum in Toxicology, Center of Environmental Health and Susceptibility, and Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural