Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schroedinger-Str. 52, 67663 Kaiserslautern, Germany.
Toxicology. 2011 Apr 11;282(3):88-93. doi: 10.1016/j.tox.2011.01.016. Epub 2011 Feb 1.
In the present investigation, the degradation of the acaricide dicofol (also known as kelthane) was investigated with special emphasis on generation of p,p'-dichlorobenzophenone (DCBP) under alkaline conditions as well as induced by UV-light. Dicofol was also incubated in the presence and absence of microsomal preparations to measure potential metabolic formation of DCBP. The results indicate that the degradation of dicofol to DCBP primarily proceeds as an abiotic process via hydroxide ion catalysed elimination of a trichloromethyl anion. The generated anion picks up a proton from the solvent to generate chloroform. Microsomal metabolism does not appear to play a major role in the degradation of dicofol. DCBP is structurally analogous to the antiandrogen p,p'-dichlorodiphenylethene (DDE). We therefore investigated whether DCBP displays antiandrogenic properties. In an in vitro transactivation system utilising transiently transfected African green monkey kidney (COS-7) cells, DCBP showed potent antiandrogenic efficacy. This finding was confirmed by further studies in T47D human mammary carcinoma cells by measuring mRNA and protein expression of androgen dependent genes i.e. TRMP-2 (testosterone-repressed prostate message-2) mRNA and PSA (prostate-specific antigen) protein.
在本研究中，特别强调了在碱性条件下以及在紫外光下，拟除虫菊酯三氯杀螨醇（也称为开乐散）的降解，同时也生成了对，对'-二氯二苯甲酮（DCBP）。还在存在和不存在微粒体制剂的情况下孵育了三氯杀螨醇，以测量 DCBP 的潜在代谢形成。结果表明，三氯杀螨醇降解为 DCBP 主要是通过氢氧根离子催化消除三氯甲基阴离子的非生物过程进行的。生成的阴离子从溶剂中获取质子以生成氯仿。微粒体代谢似乎在三氯杀螨醇的降解中不起主要作用。DCBP 在结构上与抗雄激素对，对'-二氯二苯乙烯（DDE）类似。因此，我们研究了 DCBP 是否具有抗雄激素特性。在利用瞬时转染的非洲绿猴肾（COS-7）细胞的体外转录激活系统中，DCBP 表现出很强的抗雄激素功效。这一发现通过在 T47D 人乳腺癌细胞中进一步研究，测量雄激素依赖性基因即 TRMP-2（睾酮抑制前列腺消息-2）mRNA 和 PSA（前列腺特异性抗原）蛋白的 mRNA 和蛋白表达得到了证实。
