Effects of environmental estrogenic compounds on growth of a transplanted estrogen responsive pituitary tumor cell line in rats

The modifying effects of three endocrine disrupting chemicals on the promotion phase of estrogen dependent tumor development were investigated with a transplantable rat pituitary cell line, MtT/E-2. The EDCs examined were genistein (Gen), a phytoestrogen, p-nonylphenol (NP), a surfactant and atrazine (Atz), a herbicide. Since potential exposure is through food and drinking water, oral administration was examined in the present study. Gen and NP stimulated in vitro MtT/E-2 growth at concentrations of 10−8 and 10−6 M, respectively, while Atz did not show any effects. The estrogenic activity was further confirmed by measuring transcription of an ERE-luciferase reporter transiently transfected in the cells. When MtT/E-2 cells are inoculated into ovariectomized female F344 rats, estrogen dependent tumors develop providing a simple and sensitive model to examine modulation effects of estrogenic compounds in the promotion phase. Ovariectomized F344 rats implanted with MtT/E-2 were fed diet containing NP or Gen at 25 and 250 mg/kg, or Atz at 5, 50 and 500 mg/kg. NP and Atz did not exert any modifying effects on pituitary tumor development, while Gen at 250 mg/kg exhibited a promotion influence. These results indicate that Gen might facilitate the estrogen responsive tumor development if only the promotion phase is concerned, while NP and Atz at doses used in the present study were without effect.