Linked Life Data

3345577

Source:http://linkedlifedata.com/resource/pubmed/id/3345577

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-4-14
pubmed:abstractText
1-Nitropyrene, the predominant nitropolycyclic aromatic hydrocarbon found in diesel exhaust, is a mutagen and tumorigen. 1,6-Dinitropyrene is present in diesel exhaust in much smaller quantities than 1-nitropyrene, but is much more mutagenic and carcinogenic. In an attempt to understand this difference in biological potencies, we have compared the extent of DNA binding by these two nitropyrenes in vivo. We have also determined the effect of 1-nitropyrene pretreatment upon the induction of nitroreductases and the subsequent DNA binding by both 1-nitropyrene and 1,6-dinitropyrene. Covalent DNA binding by 1-nitropyrene could not be detected in vivo; however, 1,6-dinitropyrene formed N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene as the major DNA adduct in rat liver, kidney, urinary bladder and mammary gland, with the highest levels being found in the bladder. The capability of liver microsomes to catalyze the oxidative metabolism of 1-nitropyrene was unchanged after treating rats with 8 mg/kg 1-nitropyrene. Cytochrome P-450, NADPH-cytochrome P-450 reductase and cytochrome b5 levels were also unchanged, while slight increases were detected in NADH-cytochrome b5 reductase and epoxide hydrase activities. Liver cytosolic and microsomal nitroreductase activities toward both 1-nitropyrene and 1,6-dinitropyrene were increased 2-fold, and cytosolic nitrosoreductase activity toward 1-nitrosopyrene and 1-nitro-6-nitrosopyrene was elevated by approximately 20%. DNA binding of both 1-nitropyrene and 1,6-dinitropyrene in vitro was 2-fold higher when using cytosol from 1-nitropyrene-pretreated rats. However, pretreatment of rats with 1-nitropyrene only slightly increased the amount of in vivo DNA binding by 1,6-dinitropyrene except in kidney where there was a 60% increase. These results indicate that although nitroreduction is involved in DNA adduct formation by 1,6-dinitropyrene, additional factors (e.g. O-acetylation) limit the extent of DNA binding in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
357-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
DNA binding by 1-nitropyrene and 1,6-dinitropyrene in vitro and in vivo: effects of nitroreductase induction.
pubmed:affiliation
National Center for Toxicological Research, Jefferson, AR 72079.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.