Linked Life Data

2298615

Source:http://linkedlifedata.com/resource/pubmed/id/2298615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-3-7
pubmed:abstractText
During the past 3 years, our laboratory has identified and characterized the drug SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide) as the lead compound in a series of benzotriazine di-N-oxides that are both potent and selective killers of hypoxic cells in vitro and in rodent tumors in vivo. Recently, we have identified a novel property of SR 4233: the ability of a pre- or post-irradiation drug treatment under hypoxic conditions to radiosensitize aerobic cells in culture. For the mouse cell lines RIF-1 and SCC VII in vitro, this radiosensitization took the form of a steepening of the slope of the acute dose radiation survival curve, although there was also reduced survival in the "shoulder region" of the curve. For both cell lines, the sensitization occurred whether the hypoxic drug exposure was given immediately before or after the irradiation under aerobic conditions. To determine whether radiosensitization could be demonstrated for RIF-1 and SCC VII mouse tumors in vivo, tumor-bearing animals were exposed to 4 daily dose fractions of 5 Gy of X rays either alone, or followed immediately by injections of SR 4233 and the vasoactive agent hydralazine, which increases tumor hypoxia and therefore can potentiate the effect of such hypoxiaspecific drugs. Although treatment with the SR 4233/hydralazine combination after each dose fraction reduced tumor cell survival to between 10(-5) and 10(-6), near the limits of resolution of the clonogenic survival assay, the effect appeared to be strictly additive, suggesting that with this fractionated protocol, aerobic radiosensitization could not be detected. This is likely to be a consequence of the exquisite direct cytotoxicity of the SR 4233 and hydralazine combination toward the hypoxic cells in tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0360-3016
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
125-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Aerobic radiosensitization by SR 4233 in vitro and in vivo.
pubmed:affiliation
Department of Radiation Oncology, Stanford University Medical Center, CA 94305.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.