title: [The antiandrogenic effect of dimethachlon and its mechanism].
abstract: OBJECTIVE
  To evaluate the antiandrogenic effect of heterocyclic fungicide dimethachlon and its mechanism.
  
  
  METHODS
  A combination of in vivo and in vitro assays was selected. Hershberger assay was used to determine the antiandrogenic potential of dimethachlon in vivo. Six-week-old castrated male SD rats were administrated once daily for 7 days with testosterone propionate (TP, 100 micro g/d, sc) plus gavage doses of dimethachlon (50, 100 or 200 mg x kg(-1) x d(-1)), or procymidone (150 or 300 mg x kg(-1) x d(-1), positive control), or iprodione (100 mg x kg(-1) x d(-1), positive control), or flutamide (50 mg x kg(-1) x d(-1), positive control). Transcriptional activation assay in vitro was employed to determine the mechanism of antiandrogenic activity of dimethachlon. Human hepatoma liver cells HepG2 were transiently cotransfected with human androgen receptor (AR) expression plasmid and AR-dependent luciferase report plasmid. Transfected cells were exposed to various concentrations of dimethachlon or flutamide with or without dihydrotestosterone to induce the expression of luciferase gene.
  
  
  RESULTS
  In Hershberger assay, dimethachlon, as well as other known antiandrogens, caused decrease in weight of androgen dependent organs or tissues. In 200 mg/kg group, the weight of seminal vesicle, ventral prostate, dorsolateral prostate, Cowper's gland, and levator ani plus bulbocavernosus muscles decreased by 57.8%, 44.8%, 43.9%, 30.1%, and 34.1% respectively, but did not decrease in the vehicle control group. The order of their antiandrogenic potencies was: flutamide > procymidone > dimethachlon > iprodione. In transcriptional activation assay, dimethachlon could inhibit dihydrotestosterone-dependent AR activity in transfected HepG2 cells in dose-effect relationship. The inhibiting potency of dimethachlon was about 1/100 of that of flutamide.
  
  
  CONCLUSIONS
  Dimethachlon has antiandrogenic effect, and acts as an AR antagonist. Its antiandrogenic potency is lower than flutamide and procymidone, but higher than iprodione.
authors.affiliation: Toxicology Department, Zhejiang University, Hangzhou 310031, China.
authors.forename: Guo-jun
authors.initials: GJ
authors.lastname: Zhang
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Zheng
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Zhu
authors.forename: Xin-qiang
authors.initials: XQ
authors.lastname: Zhu
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000726:Androgen Antagonists / Q000494:pharmacology* / Q000633:toxicity; D000728:Androgens / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002722:Chlorobenzenes / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005485:Flutamide / Q000494:pharmacology / Q000633:toxicity; D005659:Fungicides, Industrial / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D006827:Hydantoins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D010575:Pesticides / Q000494:pharmacology / Q000633:toxicity; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013388:Succinimides / Q000494:pharmacology* / Q000633:toxicity; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D001643:Bridged Bicyclo Compounds; D002722:Chlorobenzenes; D005659:Fungicides, Industrial; D006827:Hydantoins; D010575:Pesticides; D011944:Receptors, Androgen; D013388:Succinimides; C488805:dimethachlon; D000620:Aminoimidazole Carboxamide; D005485:Flutamide; D008156:Luciferases; C035988:procymidone; C033148:iprodione