Effect of ellagic acid and 3-O-decylellagic acid on the formation of benzo[a]pyrene-derived DNA adducts in vivo and on the tumorigenicity of 3-methylcholanthrene in mice.
Effect of ellagic acid and 3-O-decylellagic acid on the formation of benzo[a]pyrene-derived DNA adducts in vivo and on the tumorigenicity of 3-methylcholanthrene in mice.
复制标题
鞣花酸和 3-O-癸鞣酸对体内苯并[a]芘衍生的 DNA 加合物的形成以及对小鼠体内 3-甲基胆蒽致瘤性的影响。
作者：
R. Smart;M. Huang;R. Chang;J. M. Sayer;D. Jerina;A. Wood;A. Conney
采用几种不同的处理方案，评价了鞣花酸及其亲脂性更强的衍生物3-O-癸基鞣花酸对用[3 H]苯并-[a]芘（[3 H]B[a]P）处理的CD-1小鼠表皮或肺中DNA结合加合物量的影响。50 μ mol/kg鞣花酸或3-O-癸基鞣花酸与0.2 μ mol/kg [3 H]B[a]P静脉注射同时或注射前5分钟静脉注射均未抑制肺DNA结合加合物的形成。给小鼠喂食含1%鞣花酸的饲料10天，或在静脉注射0.2 μ mol/kg [3 H]B[a]P前30分钟腹腔注射120 μ mol/kg鞣花酸，均未抑制肺中DNA结合加合物的形成。在施用2、10或50 nmol [3 H]B[a]P之前5 min，将2，500 nmol鞣花酸或3-O-癸基鞣花酸施用至小鼠皮肤，对[3 H] B [a]P代谢物与表皮DNA的共价结合几乎没有影响或没有影响。用含有1%鞣花酸的饮食喂养小鼠10天，在局部剂量为2 nmol的[3 H]B[a] P后，没有抑制表皮DNA结合加合物的形成。类似地，在2 h局部施用2，500 nmol鞣花酸，应用2 nmol [~ 3 H]B[a]P前1 h和5 min及后10 min不抑制DNA结合加合物的形成，但相同的3-O-癸基鞣花酸给药方案（总剂量为10，000 nmol）导致DNA结合加合物形成的适度抑制。在CD-1或BALB/c小鼠每周两次施用1，500 nmol 3-甲基胆蒽（3-MC）前1小时局部施用1，500 nmol鞣花酸，不会抑制皮肤肿瘤的发展。我们的研究结果表明，鞣花酸和3-O-癸基鞣花酸不能有效抑制小鼠皮肤和肺中[3 H]B[a]P DNA加合物的形成，鞣花酸不能抑制3-MC诱导的BALB/c或CD-1小鼠皮肤肿瘤发生。
The effect of ellagic acid and its more lipophilic derivative, 3-O-decylellagic acid, on the amount of DNA-bound adducts in the epidermis or lung of CD-1 mice treated with [3H]benzo-[a]pyrene ([3H]B[a]P) was evaluated using several different treatment protocols. The i.v. administration of 50 mumol/kg of ellagic acid or 3-O-decylellagic acid either together with or 5 min before a 0.2 mumol/kg i.v. dose of [3H]B[a]P did not inhibit the formation of pulmonary DNA-bound adducts. Feeding mice a diet that contained 1% ellagic acid for 10 days or the i.p. administration of 120 mumol/kg of ellagic acid 30 min before the i.v. administration of 0.2 mumol/kg of [3H]B[a]P did not inhibit the formation of DNA-bound adducts in the lung. The application of 2,500 nmol of ellagic acid or 3-O-decylellagic acid to mouse skin 5 min before the application of 2, 10 or 50 nmol of [3H]B[a]P had little or no effect on the covalent binding of [3H]B[a]P metabolites to epidermal DNA. Feeding mice a diet containing 1% ellagic acid for 10 days did not inhibit the formation of epidermal DNA-bound adducts after a topical dose of 2 nmol of [3H]B[a]P. Similarly, the topical application of 2,500 nmol of ellagic acid at 2 h, 1 h and 5 min before and at 10 min after the application of 2 nmol of [3H]B[a]P did not inhibit the formation of DNA-bound adducts, but the same dosing regimen of 3-O-decylellagic acid (total dose of 10,000 nmol) resulted in a modest inhibition in the formation of DNA-bound adducts. The topical application of 1,500 nmol of ellagic acid 1 h before the application of 1,500 nmol of 3-methylcholanthrene (3-MC) to CD-1 or BALB/c mice twice weekly did not inhibit the development of skin tumors. Our results indicate that ellagic acid and 3-O-decylellagic acid are not effective in inhibiting [3H]B[a]P DNA adduct formation in mouse skin and lung and that ellagic acid does not inhibit 3-MC-induced skin tumorigenesis in BALB/c or CD-1 mice.