ANTI-MUTAGENESIS AND ANTI-PROMOTION BY APIGENIN, ROBINETIN AND INDOLE-3-CARBINOL
ANTI-MUTAGENESIS AND ANTI-PROMOTION BY APIGENIN, ROBINETIN AND INDOLE-3-CARBINOL
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DOI：
10.1093/carcin/7.6.959
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发表时间：
1986-06-01
期刊：
影响因子：
4.7
通讯作者：
BRESNICK, E
中科院分区：
文献类型：
--
作者：
BIRT, DF;WALKER, B;BRESNICK, E
我们评估了两种黄酮类化合物，芹菜素和刺槐素，以及吲哚-3-甲醇的抗诱变和抗促进特性，因为这些化合物已被报道在蔬菜中，其消费与癌症发病率降低有关。然而，这些食物的活性成分及其对致癌作用的影响尚未确定。在鼠伤寒沙门氏菌试验中，通过测量供试化合物对甲基亚硝基脲（MNU）、甲基-n-硝基-N-亚硝基胍（MNNG）、苯并[a]芘（BaP）或2-氨基蒽（2-AA）诱导的细菌致突变的影响，确定抗致突变性。包含芹菜素导致62%和43%的抑制致突变性与13 nmol的2-AA和30 nmol的BaP，分别。刺槐素对2-AA致突变性的抑制率为87%，而吲哚-3-甲醇对任何化合物的致突变性几乎没有影响。这三种化合物都不能抑制MNU或MNNG引起的诱变，并且当在不存在诱变化合物的情况下以高达20 μ g/板的剂量测试时，没有一种化合物是诱变的或有毒的。通过测量芹菜素、刺槐素和吲哚-3-甲醇对17 nmol 12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）诱导小鼠表皮中鸟氨酸脱羧酶活性（ODC）的影响来评估抗促进性质。在TPA前半小时用芹菜素、刺槐素、丁基化羟基茴香醚、13-顺式-视黄酸（均为50 μ mol）或二氟甲基鸟氨酸（1.6 μ mol）预处理皮肤，在TPA后6小时抑制ODC诱导67- 80%。此时用50 μ mol吲哚-3-甲醇预处理导致TPA诱导提高78%。用芹菜素、吲哚-3-甲醇和洋槐素进行剂量反应测量。在用12.5-100 μ mol芹菜素预处理的小鼠中，在TPA后6小时观察到30-90%的TPA诱导的ODC的抑制。用37.5或50 μ mol吲哚-3-甲醇或0.5、12.5或25 μ mol洋槐碱预处理导致TPA后6小时TPA对表皮ODC的诱导升高。然而，在TPA后6小时，用50或100 μ mol的罗比替尼处理减少了ODC诱导。在非TPA处理的小鼠皮肤中用100 μ mol芹菜素或50或100 μ mol吲哚-3-甲醇处理引起表皮ODC升高。在比较ODC诱导的时间过程中，吲哚-3-甲醇（50 μ mol）预处理将表皮ODC的诱导转移到更早的时间，除了通过TPA提高ODC诱导之外。然而，芹菜素（50 μ mol）预处理抑制TPA抑制的TPA诱导的ODC活性4、6和d8小时，表明ODC诱导没有变化。总之，吲哚-3-甲醇在本研究中没有表现出抑制诱变的潜力，并表现出增强促进的潜力。相反，芹菜素和刺槐素作为致癌作用起始和促进阶段抑制剂的潜力值得进一步研究。
We assessed the anti-mutagenic and anti-promotion properties of two flavones, apigenin and robinetin, and of indole-3-carbinol, because these compounds have been reported in vegetables, the consumption of which has been associated with reduced rates of cancer. However, the active components of these foods and their effects on carcinogenesis have not been established. Anti-mutagenicity was determined in the Salmonella typhimurium assay by measuring the effects of the test compounds on bacterial mutagenesis induced by methylnitrosourea (MNU), methyl-n-nitro-N-nitrosoguanidine (MNNG), benzo[a]pyrene (BaP) or 2-aminoanthracene (2-AA). Inclusion of apigenin resulted in a 62% and a 43% inhibition of mutagenicity with 13 nmol of 2-AA and 30 nmol BaP, respectively. Robinetin caused an 87% inhibition of mutagenicity by 2-AA, but indole-3-carbinol had little or no effect on the mutagenicity of any of the compounds. None of the three compounds inhibited mutagenesis by MNU or MNNG and none were mutagenic or toxic when tested in the absence of mutagenic compounds at doses up to 20 .mu.g/plate. Anti-promotion properties were assessed by measuring the effects of apigenin, robinetin and indole-3-carbinol on induction of ornithine decarboxylase activity (ODC) in mouse epidermis by 17 nmol 12-O-tetradecanoyl phorbol-13-acetate (TPA). Pretreatment of the skin half an hour before TPA with apigenin, robinetin, butylated hydroxyanisole, 13-cis-retinoic acid (all at 50 .mu.mol) or di-fluoromethylornithine (1.6 .mu.mol) inhibited ODC induction at 6 h after TPA by 67-80%. Pretreatment with 50 .mu.mol indole-3-carbinol caused a 78% elevation in the TPA induction at this time. Dose response measurements were conducted with apigenin, indole-3-carbinol and robinetin. Inhibition by 30-90% of TPA-induced ODC was observed at 6 h after TPA in mice pretreated with 12.5-100 .mu.mol apigenin. Pretreatment with 37.5 or 50 .mu.mol indole-3-carbinol or 0.5, 12.5 or 25 .mu.mol robinetin resulted in elevated induction of epidermal ODC by TPA at 6 h after TPA. However, treatment with 50 or 100 .mu.mol robinetin diminished ODC induction at 6 h after TPA. Treatment with 100 .mu.mol apigenin or 50 or 100 .mu.mol indole-3-carbinol in non-TPA-treated mouse skin caused elevations in epidermal ODC. In comparing the time course of ODC induction, indole-3-carbinol (50 .mu.mol) pretreatment shifted the induction of epidermal ODC to earlier times, in addition to elevating ODC induction by TPA. However, apigenin (50 .mu.mol) pretreatment inhibited TPA-inhibited TPA-induced ODC activity 4, 6 an d8 h, indicating no shift in ODC induction. In conclusion, indole-3-carbinol showed no potential for inhibition of mutagenesis in the present study and presented potential for enhancement of promotion. In contrast, the potential of apigenin and robinetin as inhibitors of the initiation and promotion phases of carcinogenesis merits further study.