Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1984-10-22
pubmed:abstractText
Isolated rat hepatocytes in early primary culture were incubated in the presence of three substituted nitroimidazoles currently of clinical interest as tumour radiosensitisers. The effects of 3h treatments with Misonidazole (MISO), Desmethylmisonidazole (DESMISO) and the basic compound Ro 03-8799 were monitored both directly from treatment and following a 24h 'recovery' period. Morphological changes were observed by SEM and TEM and included effects on the plasma membrane and the nucleus. The plasma membrane of DESMISO and 03-8799 treated cells was characterised by blebbed regions not present in control cultures, and considered indicative of an early toxic insult. Blebs were most evident in 03-8799 treated hepatocytes where they often contained coils of endoplasmic reticulum within the ground plasma. Blebbed areas were less evident 24h after the removal of the drugs from surviving cells. An increased aggregation of peripherally located heterochromatin within the nucleus was the other main morphological alteration induced by nitroimidazole treatment. This was again more prevalent in 03-8799 and DESMISO exposures; and particularly in cells demonstrating membrane damage. Parallel viability studies indicated an efficacy of the nitroimidazole towards rat liver parenchymal cells in primary culture of Ro 03-8799 greater than DESMISO greater than MISO. This fitted the order predicted from the morphological findings and from previously published clinical data. The validity of monitoring structural parameters as a means of initially indicating lesion sites following drug treatments in the hepatocyte cytotoxic screening model is considered.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0340-6075
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-76
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Morphological changes in rat hepatocytes in primary culture induced by Misonidazole, desmethylmisonidazole and Ro 03-8799.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't