Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1989-2-23
pubmed:abstractText
We have shown previously that tumor cell variants able to form experimental metastases can be generated stochastically in mouse cell lines at high rates and that, in B16 melanoma cell lines, resistance to drugs is associated with metastatic ability. Recently, we reported on the ability of two lines of KHT fibrosarcoma cells derived from individual experimental lung metastases to generate metastatic variants. The KHT 35LI cell line maintained a relatively stable high metastatic ability while the parallel line KHT 3LIc possessed a high metastatic ability when first cultured from the lung but rapidly lost this ability and became a line with a metastatic ability similar to the KHT parental line. Subsequent rate analysis indicated that the rate of generation of metastatic variants was higher for KHT 35LI cells compared to KHT 3LIc or KHT parental cells. Here we examined the ability of these two fibrosarcoma cell lines to generate variants resistant to the drugs methotrexate (MTX) and N-(phosphonacetyl)-L-aspartate (PALA). We observed that the highly metastatic KHT 35LI cell line is more resistant to these two drugs than the KHT 3LIc or the parental KHT cell lines. Cloning studies indicated that the likely reason for this increased resistance is that the KHT 35LI cell line generates variants resistant to a given concentration of MTX or PALA at higher rates than the KHT 3LIc or KHT parental cell lines. Since resistance to MTX and PALA usually arises from gene amplification, the results suggest that KHT 35LI cells possess increased ability to amplify their DNA. The association between the rates of generation of both drug-resistant and metastatic variants supports the hypothesis that the mechanism of gene amplification may be involved in the generation of both phenotypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
107-11
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Drug resistance in KHT fibrosarcoma cell lines with different metastatic ability.
pubmed:affiliation
Physics Division, Ontario Cancer Institute, Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't