Kalimi G H, Sirsat S M
Carcinogenesis. 1984 Dec;5(12):1671-7. doi: 10.1093/carcin/5.12.1671.
A previous paper reports that the potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), has a time-dependent effect on mouse epidermal gap junctions. A single topical application of 1.0 micrograms TPA results in the absence of gap junctions from mouse interfollicular epidermis between 18 and 30 h post-treatment. This paper describes the dose-dependent effect of TPA on mouse epidermis. Observations indicate that only promoting doses of TPA affect the gap junctions. Similarly, while a low dose of the hyperplasiogenic compound mezerein (1.0 microgram) is ineffective, a higher dose (4.0 micrograms) results in a significant reduction in the gap junction number. One and two applications of TPA had identical effects. The potent inhibitor of both stage I and stage II of tumor promotion, Fluocinolone acetonide, used in combination with TPA, completely suppressed the hyperplasiogenic and the gap junction modulating effects of TPA. Retinoic acid, which inhibits only stage II of tumor promotion, did not influence the gap junction eliminating property of TPA. Tosylphenylalanine chloromethyl ketone which is a mild but specific inhibitor of only stage I of tumor promotion counteracted the action of TPA on gap junctions to some extent, which remained present in smaller numbers than in normal tissue at 24 h after the treatment. These results suggest that gap junctions are essential and specifically relevant to stage I tumor promotion.
先前的一篇论文报道，强效肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）对小鼠表皮间隙连接具有时间依赖性效应。单次局部应用1.0微克TPA会导致在处理后18至30小时之间小鼠毛囊间表皮中不存在间隙连接。本文描述了TPA对小鼠表皮的剂量依赖性效应。观察结果表明，只有促进剂量的TPA会影响间隙连接。同样，虽然低剂量的增生性化合物芫花酯甲（1.0微克）无效，但较高剂量（4.0微克）会导致间隙连接数量显著减少。一次和两次应用TPA具有相同的效果。用于肿瘤促进I期和II期的强效抑制剂氟轻松丙酮与TPA联合使用时，完全抑制了TPA的增生性和间隙连接调节作用。仅抑制肿瘤促进II期的视黄酸，并未影响TPA消除间隙连接的特性。甲苯磺酰苯丙氨酸氯甲基酮是仅对肿瘤促进I期有轻度但特异性抑制作用的抑制剂，在一定程度上抵消了TPA对间隙连接的作用，在处理后24小时，间隙连接的数量仍比正常组织中的少。这些结果表明，间隙连接对于I期肿瘤促进至关重要且具有特异性相关性。
