Phospholipid peroxidation in tumor promoter-exposed mouse skin.
Phospholipid peroxidation in tumor promoter-exposed mouse skin.
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暴露于肿瘤启动子的小鼠皮肤中的磷脂过氧化。
DOI：
10.1093/carcin/15.12.2937
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发表时间：
1994
期刊：
影响因子：
4.7
通讯作者：
Marnett,LJ
中科院分区：
文献类型：
--
作者：
Beckman,JK;Bagheri,F;Ji,C;Blair,IA;Marnett,LJ
我们研究了CD1小鼠在单次或多次局部应用肿瘤促进剂12-0-十四烷基佛波醇-13-醋酸酯(TPA)后皮肤的脂质过氧化反应。在暴露于两个或更多TPA处理(间隔24-72小时)之后，羟基磷脂大量积累，达到控制值的3-5倍水平，而单次应用无效。硼氢化钠还原使产物的产率提高了约50%，这表明氧化脂质中存在额外的磷脂过氧化氢。对羟基脂肪酸组成的直相高效液相色谱分析和气相色谱/质谱仪分析表明，亚油酸的氧化衍生物，包括9-和13-羟基十八碳二烯酸(9-和13-HODE)是主要产物。立体化学分析表明，13-HODE和9-HODE的StoR立体异构体的比值分别为13和1.27，这表明TPA诱导的过氧化主要是由于自由基氧化，尽管酶(脂氧合酶)活性也可能有一定的贡献。TPA诱导的表皮的过氧化作用大于真皮。预先将小鼠皮肤暴露于抗炎剂氟喹诺酮、抗氧化剂和酶(磷脂酶A2和脂氧合酶)抑制剂，可降低随后暴露于TPA时的过氧化反应。磷脂过氧化产物可能是TPA暴露小鼠皮肤产生氧自由基的有用标记物，可能与肿瘤促进有关。
We have investigated lipid peroxidation in the skin of CD1 mice following single or repeated topical applications of the tumor promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA). A substantial accumulation of hydroxyphospholipids, to levels 3-5 times control values, followed exposure to two or more TPA treatments (24–72 h intervals), whereas single applications were ineffective. Sodium borohydride reduction increased the yield of product by approximately 50%, suggesting the additional presence of phospholipid hydroperoxides in the oxidized lipids. Straight phase HPLC analysis of the constituent hydroxy fatty acids, followed by gas chromatography/mass spectrometry, revealed that oxidized derivatives of linoleic acid, including 9- and 13-hydroxyoctadecadienoic acids (9- and 13-HODE), were the primary products. Stereochemical analysis showed ratios ofStoRstereoisomers of 13 for 13-HODE and 1.27 for 9-HODE, which implied that TPA-induced peroxidation was primarily due to free radical oxidation, although a partial contribution of enzyme (lipoxygenase) activity is possible. The TPA-induced peroxidation was greater in the epidermis than in the dermis. Pre-exposure of mouse skin to the anti-inflammatory agent fluocinolone acetonide, antioxidants and enzyme (phospholipase A2and lipoxygenase) inhibitors lowered the peroxidation response to subsequent exposure to TPA. Phospholipid peroxidation products may be useful markers of oxygen radical production in TPA-exposed mouse skin with possible relevance to tumor promotion.