Linked Life Data

1617660

Source:http://linkedlifedata.com/resource/pubmed/id/1617660

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1992-8-5
pubmed:abstractText
Acquired resistance to cisplatin has been generated in vitro in two human ovarian carcinoma cell lines: 41M, established from a previously untreated patient; and CH1, from a patient previously treated with cisplatin and cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin). In neither cell line with acquired resistance did intracellular detoxification (via increased glutathione or metallothioneins) appear to be a major determinant of resistance. Resistance in 41McisR (resistance factor of 4.7) appeared to be due predominantly to a reduced platinum accumulation (levels were only 23.8% in 41McisR versus 41M). This was also reflected at the DNA level by a similar level of reduced DNA interstrand cross-links and total platinum-DNA adducts measured immediately after a 2-h exposure to cisplatin in 41McisR versus 41M. Conversely, for CH1cisR (resistance factor of 6.5), platinum accumulation, and initial numbers of DNA-interstrand cross-links and total DNA-platinum adducts were not significantly different from the parent CH1 line. This is suggestive of a resistance mechanism involving increased DNA repair or tolerance to platinum-DNA adducts operating in the CH1cisR/CH1 pair of lines. Cross-resistance to carboplatin and partial cross-resistance to the 1,2-diaminocyclohexane-containing agent, (trans-d,l)-1,2-diaminocyclohexane tetrachloroplatinum(IV) (tetraplatin), was observed in both pairs. However, two novel platinum(IV) ammine/amine dicarboxylates, ammine dibutyratodichloro(cyclohexylamine)platinum(IV) (JM221) and ammine dibenzoatodichloro(propylamine)platinum(IV) (JM244), completely circumvented resistance in 41McisR to produce some collateral sensitivity (resistance factors of 0.67 and 0.54, respectively) but showed cross-resistance in CH1cisR (resistance factors of 3.7 and 4.6). In contrast to the data for cisplatin, intracellular platinum levels were not significantly different between the 41M and 41McisR pair of cell lines after exposure to JM244. These results suggest that the ammine/amine platinum(IV) dicarboxylates, which show considerably greater in vitro cytotoxicity than cisplatin, are capable of circumventing acquired cisplatin resistance which is due to decreased intracellular accumulation but are not able to overcome resistance at the level of DNA platination and removal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3857-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Mechanism-related circumvention of acquired cis-diamminedichloroplatinum(II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/amine platinum(IV) dicarboxylates.
pubmed:affiliation
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, England.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't