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.
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.
Uehara
N
N
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Iwahori
Y
Y
Asamoto
M
M
Baba-Toriyama
H
H
Iigo
M
M
Ochiai
M
M
Nagao
M
M
Nakayama
M
M
Degawa
M
M
Matsumoto
K
K
Hirono
I
I
Beppu
H
H
Fujita
K
K
Tsuda
H
H
D000504:Aloe; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001711:Biotransformation; D002338:Carotenoids / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D005612:Freeze Drying; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D010088:Oxidoreductases / Q000378:metabolism; D010946:Plants, Medicinal; D011804:Quinolines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D014810:Vitamin E / Q000494:pharmacology*; D019207:beta Carotene
D016587:Antimutagenic Agents; D018736:DNA Adducts; D007527:Isoenzymes; D009153:Mutagens; D011804:Quinolines; D019207:beta Carotene; D014810:Vitamin E; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D002338:Carotenoids; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2