Linked Life Data

9827584

Source:http://linkedlifedata.com/resource/pubmed/id/9827584

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-12-7
pubmed:abstractText
Recent investigations into bioreductive anticancer drugs have focused on profiling reductase enzymes and relating their expression to therapeutic activity in an approach referred to as enzyme directed drug development. However, few studies have attempted to validate this approach in vivo and even less is known about how the expression of reductases relates quantitatively and qualitatively to metabolic activation. In the present study, the antitumour activity, pharmacokinetics and metabolism of mitomycin C (MMC) has been determined in vivo in two murine adenocarcinomas of the colon, MAC 16 (high DT-diaphorase activity) and MAC 26 (low DT-diaphorase activity) after intra-tumoural injection of drug. Over a broad range of drug concentrations (50-250 microg), MAC 16 proved to be consistently the more sensitive tumour (e.g. 75 microg of MMC, T/C 11% for MAC 16 and 31% for MAC 26). Higher levels of parent drug (peak concentration 103 microg/tumour compared to 58 microg/tumour) were maintained over 45 min in MAC 16 after which time clearance was rapid from both tumours. Four metabolites were detected in both tumours characteristic of different pathways of metabolism. However, by far the major metabolite was 2,7-diaminomitosene (2,7-DM), an accurate indicator of metabolic activation of MMC. Despite higher reductase levels and greater sensitivity to the drug, there was 4-fold less production of 2,7-DM in MAC 16. These results indicate a lack of a simple relationship in vivo between reductase expression and metabolic activation and suggest factors other than pharmacological determinants being responsible for the chemosensitivity of the MAC tumours to MMC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1497-503
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Pharmacological determinants of the antitumour activity of mitomycin C.
pubmed:affiliation
Imperial Cancer Research Fund, Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
pubmed:publicationType
Journal Article