Modulation of mouse skin tumor promotion by dietary 13-cis-retinoic acid and alpha-difluoromethylornithine.
Modulation of mouse skin tumor promotion by dietary 13-cis-retinoic acid and alpha-difluoromethylornithine.
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膳食 13-顺式视黄酸和 α-二氟甲基鸟氨酸对小鼠皮肤肿瘤促进的调节。
DOI：
10.1093/carcin/7.6.1019
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
Ali,M
中科院分区：
文献类型：
--
作者：
Verma,AK;Duvick,L;Ali,M
本实验观察了饮水中添加13-顺式维甲酸（13-cis-RA）和α-二氟甲基鸟氨酸（DFMO）对12-O-十四酰佛波醇-13-乙酸酯（TPA）促进皮肤肿瘤形成的影响。分别在第一次TPA应用于雌性CD-1或SENCAR小鼠的二甲基苯并[a]蒽引发的皮肤之前1周和2天，开始在饮食中给予13-顺式-RA和在饮用水中给予DFMO。饮食13-cis-RA未能抑制肿瘤产量和发病率;在促进治疗18周时，0、5、50、100和200 mg/kg饮食13-cis-RA剂量下每只小鼠的乳头状瘤分别为25、30、22、28和25，并且在所有剂量下，100%的小鼠患有乳头状瘤。然而，饮食13-顺式-RA显着降低了TPA促进的皮肤肿瘤的大小。13-cis-RA在5、50、100和200 mg/kg饲料剂量下分别抑制每只小鼠皮肤乳头状瘤（直径> 4 mm）28、55、76和93%。维甲酸治疗不影响体重增加，所有组的存活率均超过80%。与我们以前的发现雅阁，DFMO在饮用水中给药时，是TPA促进小鼠皮肤肿瘤的非常有效的抑制剂; DFMO在0.25%浓度下抑制乳头状瘤的数量达50%。13-cis-RA（100 mg/kg）和DFMO（0.25%）饮水联合治疗对皮肤肿瘤促进的抑制作用可能是相加的。类维生素A和DFMO通过对ODC（一种与TPA促进皮肤肿瘤相关的酶）的不同作用，排除TPA增加的鸟氨酸脱羧酶（ODC）活性和腐胺积累。
The effects of dietary supplementation of 13-cis-retinoic acid (13-cis-RA) and α-difluoromethylornithine (DFMO) in the drinking water on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation was determined. Administration of 13-cis-RA in the diet and DFMO in the drinking water was started 1 week and 2 days before the first TPA application to the dimethylbenz[a]anthracene-initiated skin of either female CD-I or SENCAR mice, respectively. Dietary 13-cis-RA failed to inhibit both the tumor yield and the incidence; papillomas per mouse at 0, 5, 50, 100 and 200 mg/kg diet 13-cis-RA doses were 25, 30, 22, 28 and 25 respectively at 18 weeks of promotion treatment and at all doses 100% of the mice bore papillomas. However, dietary 13-cis-RA dramatically reduced the size of skin tumor promoted with TPA. 13-cis-RA at doses of 5, 50, 100 and 200 mg/kg diet inhibited skin papillomas (> 4 mm diameter) per mouse by 28, 55, 76 and 93%, respectively. Retinoid treatment did not affect body weight gains and the survival was more than 80% in all groups. In accord with our previous findings, DFMO when given in drinking water, was a very effective inhibitor of mouse skin tumor promotion by TPA; DFMO at 0.25% concentration inhibited the number of papillomas by 50%. Inhibition of skin tumor promotion by combined treatments with dietary 13-cis-RA (100 mg/kg) and DFMO (0.25%) in the drinking water was possibly additive. The retinoid and DFMO preclude TPA-increased ornithine decarboxylase (ODC) activity and the accumulation of putrescine by differential effects on ODC, an enzyme associated with skin tumor promotion by TPA.