Linked Life Data

4053031

Source:http://linkedlifedata.com/resource/pubmed/id/4053031

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11 Pt 1
pubmed:dateCreated
1985-12-2
pubmed:abstractText
In order to elucidate the mechanism of the metabolic activation of N-nitrosodimethylamine (NDMA), the relationship between NDMA demethylase (NDMAd) and NDMA mutagenicity in Chinese hamster V79 cells was investigated. The microsome-mediated activation system produced NDMA mutagenicity similar to the S9-mediated activation system, suggesting that microsomes are solely responsible for the activation process. Pretreatment of rats with ethanol- or acetone-induced microsomal NDMAd activity, and such treatment also enhanced microsome-mediated NDMA mutagenicity 6-7-fold. The patterns of NDMA activation by ethanol- and acetone-induced microsomes differed distinctly from that by phenobarbital-induced microsomes for both NDMAd and the mutagenicity. The former type of microsomes had a low Km for NDMA, but the latter appeared to have very high Km values, and NDMAd was highly positively related to NDMA mutagenicity. Purified cytochrome P-450 isozymes from acetone- and phenobarbital-induced microsomes, P-450ac and P-450b, respectively, were effective for the activation of NDMA to a mutagen in a reconstituted monooxygenase system. In parallel fashion to NDMAd activity, P-450ac was effective at low substrate concentrations, whereas P-450b exhibited appreciable activity only at high NDMA concentrations. The results demonstrate clearly that NDMAd, which is effectively catalyzed by a specific P-450 isozyme inducible by compounds such as ethanol, acetone, and isopropanol, is primarily responsible for the activation of NDMA to a mutagen.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5569-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Enzyme specificity in the metabolic activation of N-nitrosodimethylamine to a mutagen for Chinese hamster V79 cells.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't