Chen L C, Kirchhoff S, De Luca L M
Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892.
Cancer Lett. 1994 Apr 1;78(1-3):63-7. doi: 10.1016/0304-3835(94)90032-9.
Previously, we have shown that dietary retinoic acid (RA) at pharmacological doses (30 micrograms/g of diet) inhibited the malignant conversion of skin papillomas to carcinomas induced by a two-stage carcinogenesis protocol with 7,12-dimethylbenz[a]anthracene as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter (De Luca et al., Carcinogenesis, 14 (1993) 539-542). The purpose of this study was to determine the effect of dietary RA on skin papilloma and carcinoma formation induced by a complete carcinogenesis protocol with repeated DMBA treatment in female Sencar mice. Mice at 3 weeks of age were weaned onto a diet containing either 3 (control) or 30 (excess) micrograms of RA/g of diet and treated topically with DMBA (25.5 micrograms) once per week for 20 weeks. Mice fed excess dietary RA did not significantly differ from control mice in the following parameters: body weight, survival rate, papilloma incidence, cumulative carcinoma incidence (19.4% versus 23.7%), carcinoma yield (0.19 versus 0.26 per mouse), carcinoma conversion efficiency (5.2% versus 3.9%), and average age of carcinoma development (22.7 +/- 4.7 versus 23.3 +/- 2.8 weeks). However, papilloma yield was decreased by about 50% (i.e. 3.7 versus 7.0 at week 20, P < 0.01) between weeks 17 and 22 of age by excess dietary RA treatment. Contrary to other routes of administration (i.e. topical and systemic) of RA (Verma et al., Cancer Res., 42 (1982) 3519-3525), excess dietary RA did not enhance skin tumor formation. In addition, excess dietary RA failed to inhibit malignant conversion of papillomas to carcinomas in the complete carcinogenesis protocol. Thus, the modulation of RA on skin papilloma and carcinoma formation is dependent on carcinogenesis protocol and route of RA administration.
此前，我们已经表明，药理学剂量（30微克/克饮食）的膳食视黄酸（RA）可抑制皮肤乳头状瘤向癌的恶性转化，该转化由以7,12 - 二甲基苯并[a]蒽为引发剂、12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）为促进剂的两阶段致癌方案诱导（德卢卡等人，《癌变》，1993年第14卷，第539 - 542页）。本研究的目的是确定膳食RA对雌性Sencar小鼠经重复二甲基苯并蒽（DMBA）处理的完全致癌方案诱导的皮肤乳头状瘤和癌形成的影响。3周龄的小鼠断奶后喂食含3（对照）或30（过量）微克RA/克饮食的饲料，并每周一次局部给予DMBA（25.5微克），持续20周。喂食过量膳食RA的小鼠在以下参数方面与对照小鼠无显著差异：体重、存活率、乳头状瘤发生率、累积癌发生率（19.4%对23.7%）、癌产量（每只小鼠0.19对0.26）、癌转化效率（5.2%对3.9%）以及癌发生的平均年龄（22.7±4.7对23.3±2.8周）。然而，在17至22周龄期间，过量膳食RA处理使乳头状瘤产量降低了约50%（即20周时为3.7对7.0，P<0.01）。与RA的其他给药途径（即局部和全身给药）相反（韦尔马等人，《癌症研究》，1982年第42卷，第3519 - 3525页），过量膳食RA并未增强皮肤肿瘤形成。此外，在完全致癌方案中，过量膳食RA未能抑制乳头状瘤向癌的恶性转化。因此，RA对皮肤乳头状瘤和癌形成的调节取决于致癌方案和RA的给药途径。
