Aldaz C M, Conti C J, Chen A, Bianchi A, Walker S B, DiGiovanni J
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957.
Cancer Res. 1991 Feb 1;51(3):1045-50.
In the present study, the fate of individual papillomas induced by initiation-promotion on the backs of SENCAR mice was monitored after discontinuation of limited promoter treatment. Groups of 40 SENCAR mice each were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) at 2, 1, 0.5, or 0.25 micrograms/mouse. Animals were promoted with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly during 10 weeks. At that time point, 10 papilloma bearing mice from each group were randomly selected to follow the growth of their existing tumors. Animals and their individual tumors were identified, charted, and photographed weekly. After an initial increase, the average number of papillomas/mouse remained constant after discontinuation of TPA in all the groups except the group receiving the highest DMBA dose (Group 1) and with highest tumor load. Twenty-one weeks after TPA was discontinued, only 10-20% of the papillomas had regressed and no statistically significant differences were found among the different DMBA dose groups. On the other hand, Group 1 showed the highest percentage of coalescing tumors which was apparently a function of tumor load. In addition, no differences were observed in the proportion of positive tumors with activating point mutations at codon 61 of the Ha-ras gene when comparing samples of papillomas from the highest DMBA initiation dose group (2 micrograms) versus the lowest DMBA initiation dose group (0.25 micrograms). Our present data suggest that papillomas induced with low doses of DMBA in SENCAR mice are no more TPA dependent than those induced by higher initiating doses. Furthermore, in SENCAR mice at the doses used in the present study (0.25-2 micrograms/mouse), the number of so-called "promoter dependent" papillomas represents only a small percentage of the total papillomas produced using the initiation-promotion protocol.
在本研究中，在停止有限的启动子处理后，监测了SENCAR小鼠背部通过启动-促癌诱导的单个乳头瘤的转归。每组40只SENCAR小鼠，分别通过单次局部涂抹7,12-二甲基苯并[a]蒽（DMBA）启动，剂量为每只小鼠2、1、0.5或0.25微克。在10周内，动物每周用2微克12-O-十四烷酰佛波醇-13-乙酸酯（TPA）进行两次促癌处理。在那个时间点，从每组中随机选择10只携带乳头瘤的小鼠，以跟踪其现有肿瘤的生长情况。每周对动物及其单个肿瘤进行识别、记录和拍照。在最初增加之后，除了接受最高DMBA剂量（第1组）且肿瘤负荷最高的组之外，所有组在停止TPA处理后，每只小鼠乳头瘤的平均数量保持恒定。停止TPA处理21周后，只有10%-20%的乳头瘤消退，不同DMBA剂量组之间未发现统计学上的显著差异。另一方面，第1组显示合并肿瘤的百分比最高，这显然是肿瘤负荷的一个函数。此外，比较来自最高DMBA启动剂量组（2微克）与最低DMBA启动剂量组（0.25微克）的乳头瘤样本时，在Ha-ras基因第61密码子处具有激活点突变的阳性肿瘤比例未观察到差异。我们目前的数据表明，在SENCAR小鼠中，低剂量DMBA诱导的乳头瘤并不比高启动剂量诱导的乳头瘤更依赖TPA。此外，在本研究中使用的剂量（每只小鼠0.25-2微克）下，在SENCAR小鼠中，所谓“启动子依赖性”乳头瘤的数量仅占使用启动-促癌方案产生的总乳头瘤的一小部分。
