Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1988-3-14
pubmed:abstractText
The cytotoxicity of two series (A and B) of novel mixed-function compounds (NI-CENU) combining nitroimidazole (NI) and chloroethylnitrosourea (CENU) functions were examined in Mer- HeLa-MR and Mer+ HeLa-S3 cells. Series A compounds differed from those in Series B by having a hydroxypropyl as opposed to an ethyl group linking the imidazole ring and the nitrosoureido function. Four analogues, including the imidazole and the 2-, 4-, and 5-NO2 derivatives, were evaluated in each series. Cells were exposed to the various compounds for 4 h under aerobic and hypoxic conditions, and toxicity was assessed by clonogenic assay. Corresponding analogues in Series A and B were equally toxic to HeLa-MR cells. Preferential hypoxic toxicity was observed only with the 2-NO2 derivative in either series (I-278, Series A; I-282, Series B). For either compound a dose enhancement factor of 2.4 was observed for hypoxic exposures. The Mer+ HeLa-S3 cells were considerably more resistant to the NI-CENU than were their HeLa-MR counterparts. In further contrast to the HeLa-MR data, the Series B compounds were consistently more effective against the HeLa-S3 cells than were their corresponding Series A analogues. The enhanced effectiveness of the Series B compounds in HeLa-S3 cells may be related to the fact that these compounds express carbamoylating activity whereas Series A compounds lack this property. Again only I-278 and I-282 were preferentially toxic to hypoxic cells; however, the aerobic/hypoxic differential was dramatically reduced (dose enhancement factor = 1.3) as compared to that observed with the HeLa-MR cells. The enhanced hypoxic toxicity of the 2-NO2 NI-CENUs was not due to direct hypoxic toxicity of the nitro moiety but presumably is the result of enhancement of CENU toxicity (i.e., chemosensitization). The data suggest that much lower concentrations of NI may be required to observe chemosensitization when the NI and chemotherapeutic agent are administered as a single mixed-function compound.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
798-801
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Aerobic and hypoxic toxicity of a new class of mixed-function drugs associating nitroimidazoles and chloroethylnitrosourea in nitrosourea-sensitive (Mer-) and -resistant (Mer+) human tumor cells.
pubmed:affiliation
Department of Human Oncology, University of Wisconsin, Madison 53792.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.