Linked Life Data

12379470

Source:http://linkedlifedata.com/resource/pubmed/id/12379470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2002-10-15
pubmed:abstractText
Recently we have shown that anthraquinone food pigments such as purpurin and alizarin suppress the genotoxic activities of several mutagens including heterocyclic amines and polycyclic aromatic hydrocarbons in the Drosophila DNA repair test and in the Ames test. To investigate the mechanism of this inhibition, we have now examined the effects of these anthraquinone pigments on enzymes that metabolize xenobiotics. The activities of eight human recombinant cytochrome P450 (CYP) isozymes were measured in the presence of purpurin, alizarin or carminic acid. Purpurin and alizarin strongly inhibited the activities of CYP1A1, CYP1A2 and CYP1B1, and weakly suppressed those of CYP2A6 and CYP2E1 in a dose-dependent manner, but did not inhibit those of CYP2C19, CYP3A4 and CYP3A5. Carminic acid did not affect the activities of any CYPs tested. CYP1B1 was the most strongly affected CYP molecule by purpurin and alizarin among CYPs examined in this study. From kinetic analysis, it was shown that the inhibition by purpurin on CYP1B1 was both competitive and non-competitive, and that by alizarin was competitive. The values of slopes obtained from Lineweaver-Burk plots are proportional to the square of purpurin concentration. This observation suggests that two molecules of purpurin are interacting with one molecule of CYP1B1. The K(m) value of CYP1B1 was 11 microM, and the K(i) value of purpurin and alizarin against CYP1B1 was 0.7 microM(2) and 0.5 microM, respectively. We also examined the effects of these pigments on the mutagenicities of MeIQx and B[a]P in the Ames test, using Salmonella typhimurium TA1538 co-expressing each form of human CYP and NADPH-cytochrome P450 reductase (OR). The mutagenicity of MeIQx in TA1538 1A2/OR or 1B1/OR was suppressed by purpurin and alizarin but not by carminic acid. Purpurin also reduced the mutagenicity of B[a]P in TA1538 1A1/OR or 1B1/OR. These results suggest that the antigenotoxic activities of purpurin and alizarin can be explained by inhibition of CYP activities responsible for activating the mutagens.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,2,4-trihydroxy-9,10-anthracenedion..., http://linkedlifedata.com/resource/pubmed/chemical/2-amino-3,8-dimethylimidazo(4,5-f)qu..., http://linkedlifedata.com/resource/pubmed/chemical/Aflatoxin B1, http://linkedlifedata.com/resource/pubmed/chemical/Anthraquinones, http://linkedlifedata.com/resource/pubmed/chemical/Antimutagenic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases, http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene, http://linkedlifedata.com/resource/pubmed/chemical/Carmine, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A2, http://linkedlifedata.com/resource/pubmed/chemical/Mutagens, http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/alizarin, http://linkedlifedata.com/resource/pubmed/chemical/carminic acid, http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP1B1
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
508
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
147-56
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Inhibition of human cytochrome P450 1B1, 1A1 and 1A2 by antigenotoxic compounds, purpurin and alizarin.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't