Inhibition of cytokine production by the herbicide atrazine. Search for nuclear receptor targets.
The hematological toxicity of the commonly used triazine herbicides is a cause for concern. In a search for molecular targets of these compounds, as their effects paralleled those seen with dexamethasone (DEX), we first looked for interaction with the glucocorticoid receptor. In contrast to the effects on proliferation and cytokine production of DEX, those induced by atrazine were not prevented by the glucocorticoid antagonist RU486. Also, whereas DEX was able to inhibit the promoter activity of genes regulated by NF-kappaB, atrazine failed to do so. We next looked for interaction with members of the peroxisome proliferator-activated receptor (PPAR) family. No peroxisome proliferation was observed in the liver or kidneys of mice treated with atrazine. Moreover, no PPAR-mediated induction of promoter activity was seen on targets of PPARalpha, PPARgamma, or PPARdelta. Similarly, neither atrazine nor simazine were able to stimulate RORalpha-mediated promoter activity. Finally, no binding of atrazine to the AR was observed. In conclusion, the effects of atrazine-type herbicides most probably do not result from interaction with the above-mentioned nuclear receptors.
Devos
Sabrina
S
Pharmacology Department (FARC), Medical School, Vrije Universiteit Brussel, 103 Laarbeeklaan, B-1090 Brussel, Belgium.
De Bosscher
Karolien
K
Staels
Bart
B
Bauer
Ellinor
E
Roels
Frank
F
Vanden Berghe
Wim
W
Haegeman
Guy
G
Hooghe
Robert
R
Hooghe-Peters
Elisabeth L
EL
D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020675:Peroxisomes / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006540:Herbicides; D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D001280:Atrazine