Effects of bisphenol A-related diphenylalkanes on vitellogenin production in male carp (Cyprinus carpio) hepatocytes and aromatase (CYP19) activity in human H295r adrenocortical carcinoma cells

Journal Article · Thu Dec 01 04:00:00 EST 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.03.013· OSTI ID:20783373

Letcher, Robert J ^[1]; Sanderson, J Thomas ^[2]; Bokkers, Abraham ^[2]; Giesy, John P ^[3]; Berg, Martin van den ^[2]

---

1. National Wildlife Research Centre, Canadian Wildlife Service, Environment Canada, Ottawa, Ontario, K1A 0H3 (Canada) and Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80.176, 3508 TD Utrecht (Netherlands)
2. Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80.176, 3508 TD Utrecht (Netherlands)
3. Department of Zoology, National Food Safety and Toxicology Center, Institute of Environmental Toxicology, Michigan State University, East Lansing, MI 48824 (United States)

The present study investigated the effects of the known xenoestrogen bisphenol A (BPA) relative to eight BPA-related diphenylalkanes on estrogen receptor (ER)-mediated vitellogenin (vtg) production in hepatocytes from male carp (Cyprinus carpio), and on aromatase (CYP19) activity in the human adrenocortical H295R carcinoma cell line. Of the eight diphenylalkanes, only 4,4'-(hexafluoropropylidene)diphenol (BHF) and 2,2'-bis(4-hydroxy-3-methylphenyl)propane (BPRO) induced vtg, i.e., to a maximum of 3% to 4% (at 100 {mu}M) compared with 8% for BPA relative to the maximum induction by 17{beta}-estradiol (E2, 1 {mu}M). Bisphenol A diglycidyl ether (BADGE) was a potent antagonist of vtg production with an IC50 of 5.5 {mu}M, virtually 100% inhibition of vtg at 20 {mu}M, and an inhibitive (IC50) potency about one-tenth that of the known ER antagonist tamoxifen (IC50, 0.6 {mu}M). 2,2'-Diallyl bisphenol A, 4,4'-(1,4-phenylene-diisopropylidene)bisphenol, BPRO, and BHF were much less inhibitory with IC50 concentrations of 20-70 {mu}M, and relative potencies of 0.03 and 0.009 with tamoxifen. Bisphenol ethoxylate showed no anti-estrogenicity (up to 100 {mu}M), and 4,4'-isopropylidene-diphenol diacetate was only antagonistic at 100 {mu}M. When comparing the (anti)estrogenic potencies of these bisphenol A analogues/diphenylalkanes, anti-estrogenicity occurred at lower concentrations than estrogenicity. 4,4'-Isopropylidenebis(2,6-dimethylphenol) (IC50, 2.0 {mu}M) reduced E2-induced (EC50, 100 nM) vtg production due to concentration-dependent cytotoxicity as indicated by a parallel decrease in MTT activity and vtg, whereas the remaining diphenylalkanes did not cause any cytotoxicity relative to controls. None of the diphenylalkanes (up to 100 {mu}M) induced EROD activity indicating that concentration-dependent, CYP1A enzyme-mediated metabolism of E2, or any Ah-receptor-mediated interaction with the ER, was not a likely explanation for the observed anti-estrogenic effects. At concentrations as great as 100 {mu}M, none of the diphenylalkanes directly inhibited aromatase (CYP19) activity in H295R cells. Environmental exposure of fish to BPA and related diphenylalkanes, depending on the structure, may pose anti-estrogenic, and to a lesser extent estrogenic, risks to development and reproduction.

• OSTI ID: 20783373
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 209; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOMAS
CONTROL
ENVIRONMENTAL EXPOSURE
ENZYMES
ESTRADIOL
ETHERS
LIVER CELLS
PROPANE
RECEPTORS
TAMOXIFEN
TOXICITY