Linked Life Data

15144229

Source:http://linkedlifedata.com/resource/pubmed/id/15144229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-5-17
pubmed:abstractText
N-Nitrosamines and nitrosamides can initiate cancer. These studies evaluated the stability and reactivity of 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ) to assess its possible role in the initiation of colon cancer by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). (14)C-N-NO-IQ was incubated with different solvents and pHs in the presence and in the absence of nucleophiles and analyzed by HPLC. The products identified by electrospray ionization mass spectrometry include 2-chloro-3-methylimidazo[4,5-f]quinoline (2-Cl-IQ), 2,2'-azo-3,3'-dimethylimidazo[4,5-f]quinoline (AZO-IQ), 2-azido-IQ (2-N(3)-IQ), 3-methylimidazo[4,5-f]quinoline (deamino-IQ), and IQ. A variety of organic solvents were tested with 0.1 N HCl. 2-Cl-IQ and IQ were formed following acidification of all solvents. AZO-IQ was only formed in methanol. Deamino-IQ was the major product formed in all of the alcohols tested, except for methanol. Under acidic conditions that completely convert N-NO-IQ in 5 min (acetonitrile with 0.1 N HCl), 62% of N-NO-IQ remains after 30 min if dimethyl sulfoxide is substituted for acetonitrile. N-NO-IQ was stable in the physiologic pH range of 5.5-9.0 and did not react with nucleophiles over a 4 h period at pH 7.4 and 37 degrees C. At acidic pH (pH < or =2.0) for 30 min and 37 degrees C, N-NO-IQ becomes labile forming electrophile(s), which combine with biologically relevant nucleophiles. The reaction of N-NO-IQ at pH 2.0 followed first-order kinetics (t(1/2) = 10 +/- 2 min) and was significantly increased in 10 mM NaN(3) (t(1/2) = 2 +/- 0.1 min). 2-N(3)-IQ was the major product observed in the latter incubation. N-NO-IQ binding to DNA at pH 2.0 is 100-fold more than that at pH 7.4. At pH 2.0, greater than 90% of the binding was inhibited by 10 mM NaN(3). Thus, N-NO-IQ forms a reactive electrophile(s) at acidic pH, which binds DNA. N-NO-IQ reaction products may depend on the pH and the hydrophobic milieu of cells or tissues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
709-16
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
2-Nitrosoamino-3-methylimidazo[4,5-f]quinoline stability and reactivity.
pubmed:affiliation
Division of Geriatric Medicine, VA Medical Center, Missouri 63125, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.