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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-6-14
pubmed:abstractText
The biochemical changes responsible for acquired resistance to cisplatin (DDP) are not fully understood. We have developed DDP-resistant sublines of COLO 316 human ovarian carcinoma cells in vitro and characterized a number of biochemical features of these cells. Following selection with either continuous 50 nM DDP (COLO/DDP50 cells) or intermittent 1 microM DDP (COLO/B, COLO/C, or COLO/D cells) the onset of resistance was rapid. The resistance of the COLO/B cells gradually fell from 14-fold to 5-fold over 6 months in drug-free media. Both selection procedures produced cells exhibiting broad cross-resistance to other platinum analogs, natural products and alkylating agents. There was no significant change in the growth rate (doubling time = 36 h, cloning efficiency (28%), protein content (0.55 mg/10(6) cells), or morphology of these cells. Cell cycle distributions of log-phase cells were similar (60% G0/G1, 35% S, 5% G2/M) as determined by flow cytometry. Glutathione (GSH) levels, while not elevated in COLO-B cells at low levels of resistance (2-3-fold), were 30% elevated at higher levels of resistance (9-fold). However, GSH levels in COLO/DDP50 cells with 13-fold resistance were 2.3-fold elevated. The resistance of both cell types could be partially reversed by extended depletion of GSH with D,L-buthionine-S,R-sulfoximine. COLO/D cells had a 48% decrease in DDP accumulation at 1 h while COLO/DDP50 cells had no change in DDP accumulation. The cross-resistance profiles, GSH biochemistry and DDP accumulation data indicate that acquired DDP-resistance is a complex, multifactorial response in these cells. The specific combination of mechanisms expressed in these cells appears to depend upon the selection procedure.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0277-5379
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
619-25
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Characterization of cisplatin-resistant COLO 316 human ovarian carcinoma cells.
pubmed:affiliation
Cancer Center, University of California, San Diego, La Jolla 92093.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't