Islam T C, Toftgård R
Karolinska Institute, Center for BioTechnology at NOVUM, Huddinge, Sweden.
Toxicology. 1992 Nov 15;75(3):199-208. doi: 10.1016/0300-483x(92)90002-v.
The inhibitory effect of retinoic acid (RA) on 12-O-tetradecanoylphorbol-13-acetate- (TPA) induced mouse skin tumors was studied. Two subpopulations of tumors, small (< 2 mm) and large (> or = 2 mm) appeared after 12 weeks of cutaneous promotion by TPA (10 nmol), following initiation by application of 2 x 100 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) to the skin. RA in the doses of 17 and 34 nmol, prior to each TPA treatment inhibited (P < 0.05) the formation of small tumors at 12 weeks of promotion. However, RA in either dose did not inhibit the formation of large (> or = 2 mm) tumors. Ten weeks following withdrawal of all treatments, the number of large tumors persisted in a significantly (P < 0.05) higher number as compared to small tumors in all groups. Our results provide evidence for the existence of tumor subpopulations with a differential response to RA. In addition, elevated levels of metallothionein (MT) expression were demonstrated in papillomas induced by TPA, 72 h after the last TPA treatment. Comparing papillomas treated with RA prior to each TPA treatment and papillomas treated with TPA only, demonstrated that the elevated MT expression in papillomas was unaffected by RA. This indicated that RA did not affect the expression of a protein that showed elevated level in TPA-induced papillomas.
研究了维甲酸（RA）对12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）诱导的小鼠皮肤肿瘤的抑制作用。在通过将2×100 nmol的7,12 - 二甲基苯并[a]蒽（DMBA）涂抹于皮肤进行启动后，用TPA（10 nmol）进行12周的皮肤促癌处理，出现了两个肿瘤亚群，小肿瘤（<2 mm）和大肿瘤（≥2 mm）。在每次TPA处理前给予17和34 nmol剂量的RA，在促癌12周时抑制了（P < 0.05）小肿瘤的形成。然而，两种剂量的RA均未抑制大肿瘤（≥2 mm）的形成。在停止所有处理10周后，与所有组中的小肿瘤相比，大肿瘤的数量持续显著（P < 0.05）更高。我们的结果为存在对RA有不同反应的肿瘤亚群提供了证据。此外，在最后一次TPA处理72小时后，TPA诱导的乳头状瘤中金属硫蛋白（MT）表达水平升高。比较每次TPA处理前用RA处理的乳头状瘤和仅用TPA处理的乳头状瘤，结果表明乳头状瘤中MT表达升高不受RA影响。这表明RA不影响在TPA诱导的乳头状瘤中表达水平升高的一种蛋白质的表达。
