In vivo stimulation of DNA synthesis and induction of ornithine decarboxylase in rat colon by fatty acid hydroperoxides, autoxidation products of unsaturated fatty acids.
In vivo stimulation of DNA synthesis and induction of ornithine decarboxylase in rat colon by fatty acid hydroperoxides, autoxidation products of unsaturated fatty acids.
复制标题
通过脂肪酸氢过氧化物（不饱和脂肪酸的自氧化产物）体内刺激 DNA 合成并诱导大鼠结肠中的鸟氨酸脱羧酶。
作者：
A. Bull;N. Nigro;W. Golembieski;J. Crissman;L. Marnett
研究了直肠内滴注过氧氢和羟基脂肪酸对雄性Sprague-Dawley大鼠结肠DNA合成和鸟氨酸脱羧酶活性的影响。通过亚甲基蓝敏化的光氧化反应制备了过氧氢花生四烯酸异构体的混合物。利用大豆脂肪氧合酶作用于亚油酸，制备了13-羟基过氧-9，11-十八碳二烯酸纯品。硼氢化钠还原产生相应的羟基脂肪酸。滴注浓度高达10 mM的过氧化氢或羟基脂肪酸溶液后12小时，DNA合成以剂量依赖性方式增加，比对照值高出240%。鸟氨酸脱羧酶的诱导发生在类似的浓度范围3小时后滴入氧化亚油酸。在这种情况下，羟基酸（在10 mM时增加49倍）比氢过氧衍生物（在10 mM时增加23倍）更具刺激性。高度纯化的亚油酸和花生四烯酸没有刺激任何活性的浓度高达50 mM。这些数据表明，不饱和脂肪酸，高脂肪饮食的可能成分的自氧化产物，可以引起结肠粘膜的增殖反应。这些反应可能与高膳食脂肪对结肠癌发生的促进作用有关。
The effect of intrarectal instillation of hydroperoxy and hydroxy fatty acids on colonic DNA synthesis and ornithine decarboxylase activity in male Sprague-Dawley rats was examined. A mixture of hydroperoxy-arachidonic acid isomers was prepared by methylene blue-sensitized photooxygenation. Pure 13-hydroperoxy-9,11-octadecadienoic acid was prepared by the action of soybean lipoxygenase on linoleic acid. Sodium borohydride reduction yielded the respective hydroxy fatty acids. Twelve hr after instillation of solutions of either hydroperoxy or hydroxy fatty acids, at concentrations up to 10 mM, DNA synthesis was increased in a dose-dependent fashion up to 240% above control values. The induction of ornithine decarboxylase occurred over a similar concentration range 3 hr after instillation of oxidized linoleic acid. In this case, the hydroxy acids (49-fold increase at 10 mM), were more stimulatory than the hydroperoxy derivatives (23-fold at 10 mM). Highly purified linoleic and arachidonic acids did not stimulate either activity at concentrations up to 50 mM. These data indicate that autoxidation products of unsaturated fatty acids, likely components of high-fat diets, can evoke proliferative responses in colonic mucosa. These responses may be relevant to the promotional effect of high dietary fat on colon carcinogenesis.