Role of the estrogen receptor in the action of organochlorine pesticides on estrogen metabolism in human breast cancer cell lines.
As interest in the properties of xenoestrogenic compounds has grown, different in vitro cell culture systems have been proposed as models, against which to gauge relative estrogenic impact. Previous research indicated that some organochlorine-based pesticides elevated the production of 16 alpha-hydroxyestrone relative to 2-hydroxyestrone in ER+ MCF-7 breast cancer cells while phytochemicals like indole-3-carbinol reduced this ratio. That this ratio may be a biological marker of the risk of breast cancer has recently been demonstrated. In this study we have carried out the same paradigm in two ER- cell lines to examine the effect of receptor status. To determine whether the impact of chlorinated pesticides can be modulated by phytochemicals, the ability of indole-3-carbinol or brassinin to reverse the changes in metabolism was examined. Non-persisting phosphorus-based pesticides were also studied and shown not to have an effect on estrogen metabolism. The implications of these findings are examined.
Bradlow
H L
HL
Strang Cancer Research Laboratory, New York, NY, USA.
Davis
D
D
Sepkovic
D W
DW
Tiwari
R
R
Osborne
M P
MP
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D004784:Environmental Monitoring; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007211:Indoles / Q000494:pharmacology; D007306:Insecticides / Q000009:adverse effects* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000502:physiology*; D013859:Thiocarbamates / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000094162:Phytoalexins
D016588:Anticarcinogenic Agents; D004967:Estrogens; D007211:Indoles; D007306:Insecticides; D011960:Receptors, Estrogen; D013859:Thiocarbamates; C089020:brassinin; D000094162:Phytoalexins; C016517:indole-3-carbinol