Deng X S, Tuo J, Poulsen H E, Loft S
Department of Pharmacology, University of Copenhagen, Panum, Denmark.
Free Radic Res. 1998 Mar;28(3):323-33. doi: 10.3109/10715769809069284.
The alleged cancer preventive effects of cruciferous vegetables could be related to protection from mutagenic oxidative DNA damage. We have studied the effects of Brussels sprouts, some non-cruciferous vegetables and isolated glucosinolates on spontaneous and induced oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in groups of 6-8 male Wistar rats. Excess oxidative DNA damage was induced by 2-nitropropane (2-NP 100 mg/kg). Four days oral administration of 3 g of cooked Brussels sprouts homogenate reduced the spontaneous urinary 8-oxodG excretion by 31% (p<0.05) whereas raw sprouts, beans and endive (1:1), isolated indolyl glucosinolates and breakdown products had no significant effect. An aqueous extract of cooked Brussels sprouts (corresponding to 6.7 g vegetable per day for 4 days) decreased the spontaneous 8-oxodG excretion from 92 +/- 12 to 52 +/- 15 pmol/24 h (p<0.05). After 2-NP administration the 8-oxodG excretion was increased to 132 +/- 26 pmol/24 h (p<0.05) whereas pretreatment with the sprouts extract reduced this to 102 +/- 30 pmol/24 h (p<0.05). The spontaneous level of 8-oxodG in nuclear DNA from liver and bone marrow was not significantly affected by the sprouts extract whereas the level decreased by 27% in the kidney (p<0.05). In the liver 2-NP increased the 8-oxodG levels in nuclear DNA 8.7 and 3.8 times (p<0.05) 6 and 24 h after dose, respectively. The sprouts extract reduced this increase by 57% (p<0.05) at 6 h whereas there was no significant effect at 24 h. In the kidneys 2-NP increased the 8-oxodG levels 2.2 and 1.2 times (p<0.05) 6 and 24 h after dose, respectively. Pretreatment with the sprouts extract abolished these increases (p<0.05). Similarly, in the bone marrow the extract protected completely (p<0.05) against a 4.9-fold 2-NP induced increase (p<0.05) in the 8-oxodG level. These findings demonstrate that cooked Brussels sprouts contain bioactive substance(s) with a potential for reducing the physiological as well as oxidative stress induced oxidative DNA damage in rats. This could explain the suggested cancer preventive effect of cruciferous vegetables. The correspondence between the urinary excretion and 8-oxodG levels in 2-NP target organs supports its being the main repair product that reflects the rate of guanine oxidation in DNA.
十字花科蔬菜所谓的防癌作用可能与预防诱变的氧化性DNA损伤有关。我们以6 - 8只雄性Wistar大鼠为一组,研究了抱子甘蓝、一些非十字花科蔬菜以及分离出的硫代葡萄糖苷对自发和诱导性氧化性DNA损伤的影响,检测指标为8 - 氧代 - 7,8 - 二氢 - 2'-脱氧鸟苷(8 - 氧代脱氧鸟苷,8 - oxodG)。过量的氧化性DNA损伤由2 - 硝基丙烷(2 - NP,100 mg/kg)诱导产生。连续4天经口给予3 g煮熟的抱子甘蓝匀浆,可使自发性尿8 - 氧代脱氧鸟苷排泄量降低31%(p<0.05),而生芽甘蓝、豆类和苣荬菜(1:1)、分离出的吲哚基硫代葡萄糖苷及其分解产物则无显著影响。煮熟的抱子甘蓝水提取物(相当于4天内每天6.7 g蔬菜)可使自发性8 - 氧代脱氧鸟苷排泄量从92±12降至52±15 pmol/24 h(p<0.05)。给予2 - NP后,8 - 氧代脱氧鸟苷排泄量增加至132±26 pmol/24 h(p<0.05),而用芽提取物预处理可将其降至102±30 pmol/24 h(p<0.05)。芽提取物对肝脏和骨髓核DNA中8 - 氧代脱氧鸟苷的自发水平无显著影响,但可使肾脏中的水平降低27%(p<0.05)。在肝脏中,2 - NP分别在给药后6小时和24小时使核DNA中8 - 氧代脱氧鸟苷水平增加8.7倍和3.8倍(p<0.05)。芽提取物在6小时时可使这种增加减少57%(p<0.05),而在24小时时无显著影响。在肾脏中,2 - NP分别在给药后6小时和24小时使8 - 氧代脱氧鸟苷水平增加2.2倍和1.2倍(p<0.05)。用芽提取物预处理可消除这些增加(p<0.05)。同样,在骨髓中,提取物完全保护(p<0.05)免受2 - NP诱导的8 - 氧代脱氧鸟苷水平4.9倍的增加(p<0.05)。这些发现表明,煮熟的抱子甘蓝含有生物活性物质,有可能降低大鼠体内生理以及氧化应激诱导的氧化性DNA损伤。这可以解释十字花科蔬菜所具有的防癌作用。2 - NP靶器官中尿排泄与8 - 氧代脱氧鸟苷水平之间的对应关系支持其作为反映DNA中鸟嘌呤氧化速率的主要修复产物。