Antiproliferative effect of butyltin in MCF-7 cells.
Humans are exposed to tributyltin compounds primarily through the intake of marine food. Previous reports on toxic effects to humans are limited to a few in vitro studies giving conflicting results regarding their effects on the aromatase enzyme and androgen receptor (AR) responses. The present study evaluates the estrogenic potential of three butyltin compounds (mono-, di-, and tributyltin) in an in vitro system based on the E-Screen assay. None of the butyltin compounds tested was estrogenic in the concentration range assayed (0.01-1000 nM). However, both dibutyltin dichloride (DBT) (500 nM) and tributyltin chloride (TBT) (10 nM) inhibited 17beta-estradiol-induced cell proliferation. DBT (500 nM) and TBT (10 nM) also significantly reduced testosterone-induced cell proliferation, and the inhibition by TBT was rescued by increasing the concentration of testosterone. The present study did not confirm the inhibition of aromatase as the mechanism for an endocrine effect of butyltin compounds; moreover, the inhibition of cell proliferation by DBT and TBT occurred at concentrations at which no cytotoxicity was observed. The exact mechanism by which TBT and DBT inhibit cell proliferation remains unexplained, but it might be essentially independent of the estrogen receptor. Therefore, these compounds may not be termed classical endocrine disruptors, but rather as compounds that cause a functional anti-estrogenic response.
Nielsen
Jesper B
JB
Environmental Medicine, Institute of Public Health, University of Southern Denmark, Winsløwparken 17, DK-5000 Odense, Denmark. jbnielsen@health.sdu.dk
Rasmussen
T H
TH
D001141:Aromatase / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D009947:Organotin Compounds / Q000633:toxicity*; D013739:Testosterone / Q000032:analysis; D014407:Tumor Cells, Cultured
D009947:Organotin Compounds; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase