Comparative activity of dietary or topical exposure to three retinoids in the promotion of skin tumor induction in mice.
Comparative activity of dietary or topical exposure to three retinoids in the promotion of skin tumor induction in mice.
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发表时间：
1987-11
期刊：
影响因子：
11.2
通讯作者：
David L. McCormick;B. J. Bagg;Theresa A. Hultin
中科院分区：
文献类型：
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作者：
David L. McCormick;B. J. Bagg;Theresa A. Hultin
研究了三种类维生素A（全反式视黄酸、13-顺式视黄酸和N-（4-羟基苯基）视黄酰胺（4-HPR））作为SENCAR小鼠皮肤肿瘤诱导促进剂的饮食和局部给药活性。当作为膳食补充剂以其最大耐受剂量水平给药时，所有三种类维生素A都促进了小鼠的肿瘤发生，这些小鼠由5微克7，12-二甲基苯并（a）蒽的单次局部剂量开始。最大的促进活动，观察与饮食13-顺式-视黄酸;饮食4-HPR是显着不如视黄酸的异构体的活性。当通过局部应用给药时，全反式和13-顺式维甲酸都促进皮肤肿瘤诱导; 4-HPR没有。对接受饮食4-HPR的小鼠的皮肤样品进行HPLC分析，结果显示母体化合物和6种代谢物;在接受局部4-HPR暴露的小鼠皮肤中未发现这些代谢物，尽管4-HPR本身存在。这些数据表明，皮肤肿瘤的促进可以诱导全身给药以及局部应用的全反式和13-顺式-视黄酸。4-羟基苯基酰胺端基的取代导致促进活性的显著降低。4-HPR似乎需要代谢活化才能促进肿瘤活性;这种代谢在局部应用后不会发生在皮肤中，但在全身暴露后观察到。
The activity of dietary and topical administration of three retinoids, all-trans-retinoic acid, 13-cis-retinoic acid, and N-(4-hydroxyphenyl)retinamide (4-HPR), as promoters of skin tumor induction in SENCAR mice was studied. When administered as dietary supplements at their maximum tolerated dose levels, all three retinoids promoted tumorigenesis in mice initiated with a single topical dose of 5 micrograms 7,12-dimethylbenz(a)anthracene. Maximal promoting activity was observed with dietary 13-cis-retinoic acid; dietary 4-HPR was significantly less active than was either isomer of retinoic acid. When administered via topical application, all-trans- and 13-cis-retinoic acids both promoted skin tumor induction; 4-HPR did not. HPLC analysis of skin samples from mice receiving dietary 4-HPR showed the parent compound and six metabolites; these metabolites were not found in the skin of mice receiving topical 4-HPR exposure, although 4-HPR itself was present. These data indicate that skin tumor promotion can be induced by systemic administration as well as topical application of the all-trans- and 13-cis-retinoic acids. Substitution of a 4-hydroxyphenylamide terminal group results in a significant reduction in promoting activity. 4-HPR appears to require metabolic activation for tumor promoting activity; this metabolism does not occur in the skin following topical application, but is observed following systemic exposure.