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Decreased Levels of 2-Amino-3-methylimidazo[4,5-f]quinoline-DNA Adducts in Rats Treated with β-Carotene, α-Tocopherol and Freeze-dried Aloe
Authors:Nobuaki Uehara  Yoshio Iwahori  Makoto Asamoto  Hiroyasu Baba-Toriyama  Masaaki Iigo  Masako Ochiai  Minako Nagao  Masafumi Nakayama  Masakuni Degawa  Kazuyuki Matsumoto  Iwao Hirono  Hidehiko Beppu  Keisuke Fujita  Hiroyuki Tsuda
Affiliation:Chemotherapy, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104;Carcinogenesis Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104;Department of Hygienic Chemistry, Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980;Second Department of Pathology, Fujita Health University, School of Medicine, Kutsukakecho, Toyoake, Aichi 470-11;Institute of Pharmacognosy, Fujita Health University, Ohtoricho, Hisai, Mie 514-12
Abstract:
To assess mechanisms of chemoprevention of hepatocarcinogenesis by trans -β-carotene (β-C), DL-α-tocopherol (α-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%β-C, 1.5%α-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 β-C, α-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 β-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 β-C, and possibly also α-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.
Keywords:Chemoprevention    Hepatocarcinogenesis    Initiation    β-Carotene    IQ-DNA adduct
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