Linked Life Data

2049226

Source:http://linkedlifedata.com/resource/pubmed/id/2049226

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1991-7-22
pubmed:abstractText
This study assessed the ability of major metabolites of two types of anthracycline antibiotics, doxorubicin and idarubicin (4-demethoxydaunorubicin) to damage DNA in mouse fibrosarcoma 935.1 cells. Since DNA lesions by anthracyclines may be mediated by topoisomerase II, we also characterized the ability of the drugs to inhibit this enzyme. The C-13 alcohol and aglycone metabolites of doxorubicin and idarubicin were compared to the parent drugs in terms of induction of DNA single strand breaks measured by filter elution. In whole cells, the maximal DNA strand breakage induced by the C-13 alcohol metabolites was similar to that of their respective parent drugs. In isolated nuclei, however, the alcohol metabolites were two times more potent than the parent drugs. The aglycone metabolites produced very little damage in either whole cells or nuclei. The doxorubicin compounds differed markedly from idarubicin drugs in the way their ability to induce DNA breaks was related to cytotoxic activity. Doxorubicin and doxorubicinol cytotoxic effects (50% cell growth inhibition at 0.2 and 4 microM, respectively) coincided (in terms of drug concentrations) with the induction of significant breakage of cellular DNA. In contrast, the concentrations of idarubicin and idarubicinol needed to produce 50% growth inhibition (0.005 and 0.006 microM, respectively) were about 20 times lower than drug levels that induced significant DNA damage. All six compounds inhibited the catalytic activity of isolated topoisomerase II. While the alcohol metabolites produced this inhibition at concentrations similar to those of their parent drugs (5-10 microM), the aglycones were again much less active.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0955-3541
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
DNA damage and cytotoxicity induced by metabolites of anthracycline antibiotics, doxorubicin and idarubicin.
pubmed:affiliation
Roswell Park Cancer Institute, Grace Cancer Drug Center, Buffalo, NY 14263.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't