Gimenez-Conti I, Viaje A, Chesner J, Conti C, Slaga T J
Department of Carcinogenesis, Science Park - Research Division, University of Texas M.D. Anderson Cancer Center 78957.
Carcinogenesis. 1991 Apr;12(4):563-9. doi: 10.1093/carcin/12.4.563.
Experiments from different laboratories have shown that benzoyl peroxide (BzPo) and other organic peroxides are effective tumor promoters in the mouse skin two-stage carcinogenesis system. In the present paper we have studied the short-term effect of six other organic peroxides, which have not been previously assayed as skin tumor promoters. These compounds were chosen for their molecular diversity, the type of radical predicted to be formed, solubility and availability. The parameters evaluated in this study include a series of short-term markers of tumor promotion, hyperplasia, induction of dark basal keratinocytes and induction of ornithine decarboxylase activity. After single applications the biological activity of the compounds was: m-chloroperoxybenzoic acid greater than di-m-methylbenzoyl peroxide greater than dicumyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)mono-peroxycarbonate greater than benzoyl peroxide greater than di-m-chlorobenzoyl peroxide greater than di-t-butyl peroxide greater than t-butyl hydroperoxide. After multiple applications, the order of activity of the compounds was: dicumyl peroxide greater than di-m-methyl-benzoyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)monoperoxy carbonate greater than m-chloroperoxybenzoic acid greater than di-m-chlorobenzoyl peroxide greater than t-butyl hydroperoxide greater than benzoyl peroxide greater than di-t-butyl peroxide. The difference of activity among the different compounds did not seem to correlate directly with the chemical stability of the compound; it is more likely that the activity depends on different factors such as percutaneous absorption, metabolism, and the rate of free radical formation in vivo. The data presented here further support the association between free radicals and tumor promotion since all of the compounds, with the exception of one, were active in inducing the short-term markers of tumor promotion. It will also establish conditions for future tumor experiments.
来自不同实验室的实验表明，过氧化苯甲酰（BzPo）和其他有机过氧化物在小鼠皮肤两阶段致癌系统中是有效的肿瘤促进剂。在本文中，我们研究了其他六种有机过氧化物的短期效应，这些过氧化物之前未被作为皮肤肿瘤促进剂进行检测。选择这些化合物是基于它们的分子多样性、预计形成的自由基类型、溶解度和可得性。本研究评估的参数包括一系列肿瘤促进、增生、诱导深色基底角质形成细胞和诱导鸟氨酸脱羧酶活性的短期标志物。单次应用后，这些化合物的生物活性顺序为：间氯过氧苯甲酸＞二间甲基苯甲酰过氧化物＞二枯基过氧化物＞O,O-叔丁基-O-(2-乙基己基)单过氧碳酸酯＞过氧化苯甲酰＞二间氯苯甲酰过氧化物＞二叔丁基过氧化物＞叔丁基过氧化氢。多次应用后，化合物的活性顺序为：二枯基过氧化物＞二间甲基苯甲酰过氧化物＞O,O-叔丁基-O-(2-乙基己基)单过氧碳酸酯＞间氯过氧苯甲酸＞二间氯苯甲酰过氧化物＞叔丁基过氧化氢＞过氧化苯甲酰＞二叔丁基过氧化物。不同化合物之间的活性差异似乎与化合物的化学稳定性没有直接关联；活性更可能取决于不同因素，如经皮吸收、代谢以及体内自由基形成的速率。此处呈现的数据进一步支持了自由基与肿瘤促进之间的关联，因为除一种化合物外，所有化合物在诱导肿瘤促进的短期标志物方面均有活性。这也将为未来的肿瘤实验奠定基础。
