Characterization of the antitumor-promoting activity of camptothecin in SENCAR mouse skin.
Characterization of the antitumor-promoting activity of camptothecin in SENCAR mouse skin.
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喜树碱在 SENCAR 小鼠皮肤中的抗肿瘤促进活性的表征。
DOI：
10.1093/carcin/17.5.1141
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发表时间：
1996
期刊：
影响因子：
4.7
通讯作者：
Perchellet,JP
中科院分区：
文献类型：
--
作者：
Gao,XM;Perchellet,EM;Davis,AW;Newell,SW;Hua,DH;Perchellet,JP
（+）-喜树碱（CPT）是一种对S期细胞具有特异性毒性的拓扑异构酶I抑制剂，在senar小鼠中局部测试了其抑制7,12-二甲基苯[a]蒽（DMBA）引发皮肤肿瘤和12- 0-十四烷基酚-13-乙酸（TPA）完全促进肿瘤的能力。尽管CPT不能阻止亚致癌剂量的DMBA与DNA的共价结合，但它可以增强由该引发剂引起的DNA合成的早期抑制，并可能降低DNA复制在肿瘤起始中的重要作用。事实上，CPT （400 nmol）在DMBA之前4小时或之后1小时应用，抑制了该化合物引发的皮肤肿瘤的产量，但没有抑制其发生率。此外,因为它能抑制DNA合成TPA-stimulated 16 h应用12 h后肿瘤促进剂,CPT部分减少肿瘤起始DMBA时16 h后TPA预处理CPT (400 nmol)应用1 h之前或4、12、24和48 h后每个促销TPA治疗显著抑制皮肤肿瘤的发病率和收益率由该代理CPT延误和抑制促进皮肤肿瘤最当应用每个TPA治疗后12 - 24小时,有时它可以阻断TPA引起的早期抑制期后的DNA合成刺激。25、100和400 nmol CPT治疗后抑制皮肤肿瘤促进的能力是剂量依赖性的。在TPA（1期）-mezerein（2期）方案中，CPT （400 nmol）治疗后抑制肿瘤促进的第一阶段和第二阶段，这与CPT降低第1阶段和第2阶段所需的DNA和鸟氨酸脱羧酶反应的能力有关。因此，多阶段皮肤癌变的经典模型可能对确定新型CPT类似物在抑制肿瘤发生、促进和进展方面是否比其母体化合物更有效有价值。
(+)-Camptothecin (CPT), a topoisomerase I inhibitor specifically toxic toward S phase cells, was tested topically for its ability to inhibit skin tumor initiation by 7,12-dimethylbenz[a]anthracene (DMBA) and complete tumor promotion by 12–0-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Even though CPT does not prevent the covalent binding of a subcarcinogenic dose of DMBA to DNA, it enhances early inhibition of DNA synthesis caused by this initiator and may decrease the essential role of DNA replication in tumor initiation. Indeed, CPT (400 nmol) applied 4 h before or 1 h after DMBA inhibits the yield, but not the incidence, of skin tumors initiated by this compound. Moreover, because it inhibits TPA-stimulated DNA synthesis at 16 h when applied 12 h after the tumor promoter, CPT partially decreases tumor initiation when DMBA is applied 16 h after a TPA pre-treatment CPT (400 nmol) applied 1 h before or 4, 12, 24 or 48 h after each promotion treatment with TPA remarkably inhibits the incidence and yield of skin tumors promoted by this agent CPT delays and inhibits promotion of skin tumors the most when applied 12–24 h after each TPA treatment, at times when it can block the stimulation of DNA synthesis that follows the period of early inhibition caused by TPA. The ability of post-treatments with 25, 100 and 400 nmol CPT to inhibit skin tumor promotion is dose dependent. In the TPA (stage l)-mezerein (stage 2) protocol CPT (400 nmol) post-treatment inhibits both the first and second stages of tumor promotion, related to its ability to decrease the DNA and ornithine decarboxylase responses required for stages 1 and 2 respectively. The classic model of multistage skin carcinogenesis, therefore, may be valuable to determine if novel CPT analogs are more effective than their parent compound at inhibiting tumor initiation, promotion and progression.