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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-8-20
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pubmed:abstractText |
Dietary restriction (DR) alters the activities of hepatic drug metabolizing enzymes and modulates the formation of carcinogen-DNA adducts in carcinogen treated animals. Our previous results showed that a 40% restriction of diet (60% of ad libitum (AL) food consumption) reduced the hepatic metabolic activation of aflatoxin B1 (AFB1) but increased the activation of benzo[a]-pyrene (BaP) in both rats and mice. In this study, the focus was directed toward the levels of carcinogen-DNA adducts formation and the carcinogen-induced DNA strand breaks in mouse kidney and liver DNA. DR significantly inhibited both AFB1-DNA adduct formation and AFB1-induced DNA strand breaks in kidney DNA of mice that received a single dose of [3H]AFB1 (5 mg/kg). The levels of AFB1-DNA adduct formation in mouse kidney DNA correlated well with increased AFB1-induced DNA strand breaks. The correlation between the levels of AFB1-DNA-adducts formed and DNA strand breaks in kidney DNA of DR-mice was less linear than between its AL-counterpart suggesting that other factors, such as different rates of DNA repair, may be involved. In addition, DR enhanced hepatic BaP- and 6-nitrochrysene (6-NC)-DNA adduct formation in the mice treated with BaP and 6-NC, respectively. The formation of the specific BaP-adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (N2-dG-BaP), in mouse liver was proportional to the dose, and was compatible to the BaP-induced DNA strand breaks affected by DR. The enhancement of the total 6-NC-DNA adduct formation in DR-mouse was also in correlation with the increased 6-NC-induced DNA strand breaks. The activity of mouse liver microsomal nitro-reductase increased by 2-fold in response to DR indicating that the nitroreduction may contribute to the increase of the metabolic activation of 6-NC. Our present results indicate that the effect of DR on the carcinogen activation is dependent upon the DR-modulated carcinogen metabolizing enzyme activities.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-nitropyrene reductase,
http://linkedlifedata.com/resource/pubmed/chemical/6-nitrochrysene,
http://linkedlifedata.com/resource/pubmed/chemical/Aflatoxin B1,
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Chrysenes,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroreductases
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0378-4274
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21-30
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9242354-Aflatoxin B1,
pubmed-meshheading:9242354-Animals,
pubmed-meshheading:9242354-Benzo(a)pyrene,
pubmed-meshheading:9242354-Biotransformation,
pubmed-meshheading:9242354-Carcinogens,
pubmed-meshheading:9242354-Chrysenes,
pubmed-meshheading:9242354-DNA Adducts,
pubmed-meshheading:9242354-DNA Damage,
pubmed-meshheading:9242354-Food Deprivation,
pubmed-meshheading:9242354-Kidney,
pubmed-meshheading:9242354-Liver,
pubmed-meshheading:9242354-Male,
pubmed-meshheading:9242354-Mice,
pubmed-meshheading:9242354-Microsomes, Liver,
pubmed-meshheading:9242354-Mutagens,
pubmed-meshheading:9242354-Nitroreductases,
pubmed-meshheading:9242354-Rats
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pubmed:year |
1997
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pubmed:articleTitle |
Dietary restriction modulated carcinogen-DNA adduct formation and the carcinogen-induced DNA strand breaks.
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pubmed:affiliation |
National Center for Toxicological Research, Jefferson, AR 72079, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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