Enhancement of mezerein-promoted papilloma formation by treatment with 12-O-tetradecanoylphorbol-13-acetate or mezerein prior to initiation.
Enhancement of mezerein-promoted papilloma formation by treatment with 12-O-tetradecanoylphorbol-13-acetate or mezerein prior to initiation.
复制标题
在开始前用 12-O-十四烷酰佛波醇-13-乙酸酯或 mezerein 治疗可增强 mezerein 促进的乳头状瘤形成。
DOI：
10.1093/carcin/9.3.405
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发表时间：
1988
期刊：
影响因子：
4.7
通讯作者：
DiGiovanni,J
中科院分区：
文献类型：
--
作者：
Ewing,MW;Crysup,SE;Phillips,JL;Slaga,TJ;DiGiovanni,J
在SENCAR小鼠中检查启动子处理在开始之前对随后通过美泽瑞因的促进的影响。各组小鼠接受两次不同的完全以及第一和第二阶段启动子的应用，在起始前的不同时间间隔给予，范围为3天至10周。然后用2 yg的7，12-二甲基苯并[a]蒽（DMBA）开始小鼠，2周后用2 yg的美泽瑞因每周两次治疗。在启动前3天、1、2、3或5周接受2 μ g 12-O-十四酰基佛波醇-13-乙酸酯（TPA）预处理的小鼠中的乳头状瘤反应与在启动后在促进阶段I期间给予TPA随后在用美泽瑞因促进阶段II期间所观察到的相似（所有组中每只小鼠4-5个乳头状瘤）。令人惊讶的是，在启动前2周或5周用II期启动子美泽瑞因（2 μg）预处理也产生了与用标准两阶段促进方案诱导的类似的乳头状瘤应答（每只小鼠分别为4.7和6.4个乳头状瘤）。乳头状瘤反应低于标准的两阶段促进方案，即在启动前2周或5周给予I期启动子A23187（80 μg/小鼠）预处理（每只小鼠分别有2.6和2.3个乳头状瘤）。然而，在开始前2周给予较高剂量A23187（160 μg/小鼠）的重复实验（目前正在进行中）表明其比80 μg剂量更有效。当预处理和开始之间的时间间隔增加到10周时，TPA和A23187预处理的乳头状瘤反应减少到每只小鼠低于两个乳头状瘤，而美泽瑞因预处理减少到每只小鼠低于三个乳头状瘤，表明效果是可逆的。接受这些化合物的两次应用的小鼠表皮的组织学变化与肿瘤反应相关。在这方面，TPA和美泽瑞因两次给药导致相似程度的表皮增生（表皮厚度分别为53.5 ± 1.5和50.0 ± 1.1 μm）。用80 μg A23187（39.4 ± 1.8 μm）处理两次所产生的增生明显减少，还检测了用过氧化苯甲酰（20 mg）和大黄素（50μg）预处理对美泽瑞因随后促进活性的影响。在开始前2或5周用这些化合物预处理导致随后用美泽瑞因促进的肿瘤反应，与在开始前接受丙酮的小鼠组相似（每只小鼠1-2个乳头状瘤）。这些结果表明，在开始前通过预处理增强美泽瑞因促进的能力不是所有类型的皮肤肿瘤促进剂的一般性质。这种作用的可逆性的时间过程和与诱导的增生的相关性支持TPA、美泽瑞因和A23187可以影响在启动前操作上被称为I期促进的假设。
The effects of promoter treatments prior to initiation on subsequent promotion by mezerein were examined in SENCAR mice. Groups of mice received two applications of various complete as well as first and second stage promoters given at various time intervals prior to initiation ranging from 3 days to 10 weeks. The mice were then initiated with 2 μg of 7,12-dimethylbenz[a]anthracene (DMBA) followed 2 weeks later by twice-weekly treatments with 2 μg of mezerein. The papilloma response in mice, receiving pretreatments with 2 μgof 12-O-tetradecanoylphorbol-13-acetate (TPA) either 3 days, 1, 2, 3 or 5 weeks before initiation, was similar to that seen when TPA was given after initiation during stage I of promotion followed by stage II of promotion with mezerein (4-5 papillomas per mouse in allgroups). Surprisingly, pretreatment with the stage II promoter, mezerein (2 μg), either 2 or 5 weeks prior to initiation, also gave papilloma responses similar to that induced with the standard two-stage promotion protocol (4.7 and 6.4 papillomas per mouse, respectively). The papilloma response was less than that in the standard two-stage promotion protocol when pretreatments with the stage I promoter A23187 (80 μg/mouse) were given either 2 or 5 weeks before initiation (2.6 and 2.3 papillomas per mouse, respectively). However, a repeat experiment (currently in progress) with a higher dose of A23187 (160 μg/mouse) given 2 weeks prior to initiation indicates that it is more effective than the 80 μg dose. When the time interval between pretreatment and initiation was increased to 10 weeks, the papilloma response with TPA and A23187 pretreatment was reduced to below two papillomas per mouse and with mezerein pretreatment to below three papillomas per mouse, indicating the effect was reversible. Histological changes in epidermis of mice which received two applications of these compounds correlated with the tumor response. In this regard, treatment with two applications of TPA and mezerein resulted in an epidermal hyperplasia of similar magnitude (epidermal thickness of 53.5 ± 1.5 and 50.0 ± 1.1 μm, respectively). The hyperplasia produced by treatment with two applications of 80 μg A23187 (39.4 ± 1.8 μm) was significantly less. The ability of pretreatments with benzoyl peroxide (20 mg) and chrysarobin (50μg) to affect the subsequent promoting activity of mezerein was also examined. Pretreatmentsat2 or 5 weeks before initiation with these com pounds resulted in a tumor response upon subsequent promotion with mezerein similar to the groups of mice which received acetone prior to initiation (1-2 papillomas per mouse). These results indicate that the ability to enhance promotion with mezerein by pretreatments prior to initiation is not a general property of all classes of skin tumor promoters. The time-course for reversibility of this effect and the correlation with induced hyperplasia support the hypothesis that TPA, mezerein and A23187 can effect what has been operationally referred to as stage I promotion prior to Initiation.