Linked Life Data

7866988

Source:http://linkedlifedata.com/resource/pubmed/id/7866988

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-3-30
pubmed:abstractText
The role of human cytochromes P4501A1, -1A2, -3A4, and -3A5 in the metabolism of the polycyclic aza-aromatic hydrocarbons 7-methylbenz(c)acridine and dibenz(aj)acridine was investigated. The regioselectivity of the reactions was determined, as well as the associated stereoselectivity in the production of dihydrodiol metabolites and K-region oxides. Metabolite distributions were also examined in the presence of the epoxide hydrolase inhibitor 1,1,1-trichloropropylene-2,3-oxide and the P450 modulator alpha-naphthoflavone. P4501A2 was most regioselective for the production of the proximate carcinogen; the 3,4-dihydrodiol of 7-methylbenz(c)acridine and P4503A4 showed the highest regioselectivity for K-region oxidation. In contrast, the analogous putative proximate carcinogen of dibenz(aj)acridine was formed with the highest relative abundance by P4503A4, while P4501A2 was most regioselective for K-region oxidation. For both compounds the proximate carcinogens possessed predominantly the 3R,4R-absolute configuration, independent of the P450 catalyzing the reaction. The K-region dihydrodiols of 7-methylbenz(c)acridine were formed with no stereoselectivity, except with P4501A2 which favored production of the S,S isomer. In contrast the K-region dihydrodiol of dibenz(aj)acridine was formed by P4501A1 and P4501A2 as the R,R isomer with almost 100% optical purity. P4501A2 and 3A4 showed no stereoselectivity in the formation of the K-region oxide of 7-methylbenz(c)acridine, while P4501A1 produced the 5R,6S-oxide with low optical purity. For dibenz(aj)acridine 5,6-oxide, P4501A1 predominantly formed 5S,6R-oxide (80% pure). These results emphasize the importance of the composition and levels of expressed P450s of an individual in relation to the activation and detoxification of toxicants.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1052-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Metabolism of polycyclic aza-aromatic carcinogens catalyzed by four expressed human cytochromes P450.
pubmed:affiliation
Department of Pharmacy, University of Sydney, New South Wales, Australia.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't