Document Detail

Decreased levels of 2-amino-3-methylimidazo[4,5-f]quinoline-DNA adducts in rats treated with beta-carotene, alpha-tocopherol and freeze-dried aloe.
MedLine Citation:
PMID:  8641964     Owner:  NLM     Status:  MEDLINE    
To assess mechanisms of chemoprevention of hepatocarcinogenesis by trans-beta-carotene (beta-C), DL-alpha-tocopherol (alpha-T), and freeze-dried whole leaves of Kidachi aloe (Aloe), formation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adducts was measured by 32P-post-labeling analysis, and CYP1A1 and CYP1A2 protein levels were analyzed by ELISA. Group 1 rats were fed diet containing 0.02% beta-C, 1.5% alpha-T or 30% Aloe over an 8-day period, while group 2 was given basal diet alone. On day 7, all animals were subjected to two-thirds partial hepatectomy (PH). Twelve hours after PH, they received a single dose of the carcinogenic food pyrolysate IQ (100 mg/kg) intragastrically, to initiate hepatocarcinogenesis. Rats were killed 6, 12, 24 and 48 h after IQ administration. The levels of adducts, expressed as relative adduct labeling values in rats treated with beta-C, alpha-T and Aloe, were decreased as compared with the control group at hour 24 (36 h after PH), with a significant difference in the case of the beta-C group (46.4% of the control value). Similarly, all showed a tendency for decrease at hour 48. Furthermore, the levels of CYP1A2, known to be responsible for activation of IQ, showed a significant reduction at hour 24. It is concluded that beta-C, and possibly also alpha-T and Aloe, have the potential to reduce IQ-DNA adduct formation, presumably as a result of decreased formation of active metabolites. The results may explain, at least in part, the previously observed inhibitory effects of these compounds on induction of preneoplastic hepatocellular lesions.
N Uehara; Y Iwahori; M Asamoto; H Baba-Toriyama; M Iigo; M Ochiai; M Nagao; M Nakayama; M Degawa; K Matsumoto; I Hirono; H Beppu; K Fujita; H Tsuda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Japanese journal of cancer research : Gann     Volume:  87     ISSN:  0910-5050     ISO Abbreviation:  Jpn. J. Cancer Res.     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-07-17     Completed Date:  1996-07-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8509412     Medline TA:  Jpn J Cancer Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  342-8     Citation Subset:  IM    
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
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MeSH Terms
Antimutagenic Agents / pharmacology*
Carotenoids / pharmacology*
Cytochrome P-450 CYP1A2
Cytochrome P-450 Enzyme System / metabolism
DNA / drug effects,  metabolism
DNA Adducts / metabolism*
DNA Damage
Freeze Drying
Isoenzymes / metabolism
Mutagens / metabolism*,  pharmacokinetics,  toxicity*
Oxidoreductases / metabolism
Plants, Medicinal*
Quinolines / metabolism*,  pharmacokinetics,  toxicity*
Rats, Inbred F344
Vitamin E / pharmacology*
beta Carotene
Reg. No./Substance:
0/Antimutagenic Agents; 0/DNA Adducts; 0/Isoenzymes; 0/Mutagens; 0/Quinolines; 1406-18-4/Vitamin E; 36-88-4/Carotenoids; 7235-40-7/beta Carotene; 76180-96-6/2-amino-3-methylimidazo(4,5-f)quinoline; 9007-49-2/DNA; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Oxidoreductases; EC P-450 CYP1A2

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