Verma A K, Duvick L, Ali M
Carcinogenesis. 1986 Jun;7(6):1019-23. doi: 10.1093/carcin/7.6.1019.
The effects of dietary supplementation of 13-cis-retinoic acid (13-cis-RA) and alpha-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-1 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 (greater than 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.
研究了饮食中补充13 - 顺式视黄酸（13 - cis - RA）和饮用水中添加α - 二氟甲基鸟氨酸（DFMO）对12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）促进的皮肤肿瘤形成的影响。分别在首次将TPA涂抹于雌性CD - 1或SENCAR小鼠经二甲基苯并[a]蒽诱发的皮肤前1周和2天开始在饮食中给予13 - cis - RA以及在饮用水中给予DFMO。饮食中的13 - cis - RA未能抑制肿瘤产量和发病率；在促癌治疗18周时，饮食中13 - cis - RA剂量为0、5、50、100和200 mg/kg时，每只小鼠的乳头状瘤数量分别为25、30、22、28和25个，且所有剂量组中100%的小鼠都有乳头状瘤。然而，饮食中的13 - cis - RA显著减小了TPA促进形成的皮肤肿瘤的大小。饮食中13 - cis - RA剂量为5、50、100和200 mg/kg时，每只小鼠直径大于4 mm的皮肤乳头状瘤分别减少了28%、55%、76%和93%。类视黄醇治疗不影响体重增加，所有组的存活率均超过80%。与我们之前的研究结果一致，饮用水中添加DFMO是TPA促进小鼠皮肤肿瘤形成的非常有效的抑制剂；浓度为0.25%的DFMO可使乳头状瘤数量减少50%。饮食中13 - cis - RA（100 mg/kg）与饮用水中DFMO（0.25%）联合治疗对皮肤肿瘤促进的抑制作用可能具有相加性。类视黄醇和DFMO通过对鸟氨酸脱羧酶（ODC）产生不同影响，该酶与TPA促进皮肤肿瘤形成有关，从而阻止TPA增加ODC活性和腐胺的积累。
