title: Dicofol degradation to p,p'-dichlorobenzophenone - a potential antiandrogen.
abstract: 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.
authors.affiliation: Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schroedinger-Str. 52, 67663 Kaiserslautern, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Thiel
authors.forename: Sabine
authors.initials: S
authors.lastname: Guth
authors.forename: Sonja
authors.initials: S
authors.lastname: Böhm
authors.forename: Gerhard
authors.initials: G
authors.lastname: Eisenbrand
mesh_terms: D000726:Androgen Antagonists / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001577:Benzophenones / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D019556:COS Cells; D002417:Cattle; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D051152:Clusterin / Q000235:genetics / Q000378:metabolism; D004010:Dicofol / Q000378:metabolism / Q000633:toxicity*; D005822:Genetic Vectors; D006801:Humans; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010957:Plasmids; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D001577:Benzophenones; D051152:Clusterin; D007306:Insecticides; D012333:RNA, Messenger; D011944:Receptors, Androgen; C004759:4,4'-dichlorobenzophenone; D017430:Prostate-Specific Antigen; D004010:Dicofol