Estrogenic effects of environmental chemicals: an interspecies comparison.
The development of various in vitro screening methods has led to identification of novel estrogenic chemicals of natural and anthropogenic origin. In this study, the (anti)estrogenic potential of several environmental chemicals were compared in an array of in vitro test systems comprising: (i) competitive binding to estrogen receptors derived from the human breast cancer cell line MCF-7 (hER) and rainbow trout (Oncorhynchus mykiss) (rtER), (ii) a proliferation assay with MCF-7 cells (E-SCREEN), and iii) induction of vitellogenin (rtVtg) in isolated rainbow trout hepatocytes. The results showed substantial differences in assay sensitivity for potent estrogens like 17beta-estradiol, diethylstilbestrol and zearalenone (ranking order of sensitivity: E-SCREEN > hER approximately rtER approximately rtVtg). Chemicals like 4-n-nonylphenol and bisphenol A had higher relative binding affinity to the hER, whereas 4-t-butylphenol and 4-n-butylphenol showed highest affinity to the rtER. Zearalenone and the novel estrogen 4-t-butylhexanol displayed a considerable higher relative potency in the E-SCREEN than the rtVtg assay, whereas alkylphenols and the novel estrogen mimic 4-t-butyl-nitrobenzene were most potent in fish cells. Correlation analysis of data from the test systems suggest that interspecies differences is largely due to inter-assay variation of the ER-dependent cellular responses, whereas binding to the ER are fairly similar in the two species tested.
Olsen
Christel M
CM
Norwegian Institute of Public Health, Division of Environmental Medicine, N-0403 Oslo, Norway. christel.olsen@veths.no
Meussen-Elholm
Elise T M
ET
Hongslo
Jan K
JK
Stenersen
Jørgen
J
Tollefsen
Knut-Erik
KE
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001681:Biological Assay; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D014819:Vitellogenins / Q000378:metabolism
D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D014819:Vitellogenins