Inhibition of 17 beta-estradiol and progesterone activity in human breast and endometrial cancer cells by carbamate insecticides.
Using a combination of in vitro assays we have examined the capacities of contemporary-exposure chemicals to modulate human estrogen and human progesterone receptor (hER and hPR) activity in human breast and endometrial cancer cells. The carbamate insecticides aldicarb, Baygon (propoxur), bendiocarb, carbaryl, methomyl, and oxamyl were used in this study. The carbamates alone weakly activated estrogen- or progesterone-responsive reporter genes in breast and endometrial cancer cells. All of the carbamates decreased estradiol- or progesterone-induced reporter gene activity in the breast and endometrial cancer cells. In whole cell competition binding assays, the carbamates demonstrated a limited capacity to displace radiolabeled estrogen or progesterone from ER or PR. Based on the results presented here, the carbamate insecticides may represent a class of chemicals which function through a mechanism separate from ligand-binding and, therefore, may act as general endocrine modulators in mammalian cells.
Klotz
D M
DM
Tulane-Xavier Center for Bioenvironmental Research-Environmental Endocrinology Project, New Orleans, LA 70122, USA. dklotz@mailhost.tcs.tulane.edu
Arnold
S F
SF
McLachlan
J A
JA
D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D002219:Carbamates; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D011374:Progesterone / Q000037:antagonists & inhibitors*; D045167:Progesterone Congeners / Q000378:metabolism; D011397:Promegestone / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism*
D002219:Carbamates; D004965:Estrogen Antagonists; D007306:Insecticides; D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D011397:Promegestone; D008156:Luciferases