Linked Life Data

8222071

Source:http://linkedlifedata.com/resource/pubmed/id/8222071

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1993-12-1
pubmed:abstractText
We assessed the possible role of the human repair genes, ERCC1 and ERCC3, in resistance to cisplatin-induced cytotoxicity. The UV repair-deficient Chinese hamster ovary (CHO) 43:3B [designated ERCC1(-)] cell line and its paired subline 83-J5, which is stably transfected with the human DNA excision repair gene ERCC1 [designated ERCC1(+)], were used in this study. UV repair-deficient CHO 27-1 cells [designated ERCC3(-)] and its paired subline designated 'ERCC3(+)', which is stably transfected with the human DNA excision repair gene ERCC3, were also used. In each pair of cell lines, we assessed cisplatin cytotoxicity, cellular drug accumulation and platinum-DNA adduct repair after 1 h drug exposures. Drug accumulation and DNA repair were assessed by atomic absorption spectrometry with Zeeman background correction. ERCC1(+) cells (IC50 = 4.0 microM) were 5-fold more resistant to cisplatin than ERCC1(-) cells (IC50 = 0.75 microM). ERCC1(+) cells repaired 25% of DNA lesions in cellular DNA within a 6 h time period following an IC50 drug exposure and repaired 48% over 24 h. No DNA repair was observed in ERCC1(-) cells during the same time periods. Both cell lines showed similar patterns of drug accumulation. For ERCC3(-) cells (IC50 = 54 microM) and ERCC3(+) cells (IC50 = 49 microM), the profiles of cisplatin sensitivity and cellular drug accumulation were similar. When treated with 50 microM cisplatin, these cells showed similar patterns of drug accumulation, and were equally efficient at forming and repairing lesions in cellular DNA. These data show that in UV repair-deficient CHO cells, ERCC1 confers resistance to cisplatin and confers the ability to remove platinum from cellular DNA. In contrast, ERCC3 does not influence cisplatin drug sensitivity or adduct repair capability. This suggests that ERCC1 may be a determinant of cisplatin resistance, whereas ERCC3 is probably not.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:geneSymbol
ERCC1, ERCC3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2177-80
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Cisplatin sensitivity/resistance in UV repair-deficient Chinese hamster ovary cells of complementation groups 1 and 3.
pubmed:affiliation
Medical Ovarian Cancer Section, National Cancer Institute, Bethesda, MD 20892.
pubmed:publicationType
Journal Article