Specific in vitro toxicity of crude and refined petroleum products: II. Estrogen (alpha and beta) and androgen receptor-mediated responses in yeast assays.
The present study is the second in a series aiming at a systematic inventory of specific toxic effects of oils. By employing a recombinant yeast stably transfected with human estrogen receptor-alpha (ERalpha) or -beta (ERbeta) or androgen receptor (AR) and expressing yeast enhanced green fluorescent protein, the (anti-)estrogenicity and (anti-)androgenicity of 11 crude oils and refined products were studied. None of the oils tested had significant estrogenic effects in the ERalpha assay or androgenic effects in the AR assay. However, all oils were capable of inducing estrogenic responses in the ERbeta assay, with several responses being above even the maximal response of the standard 17beta-estradiol (E2). Based on the lowest effect concentrations, the potencies of oils in all the assays were between four and seven orders of magnitude lower than those of the standards E2 or testosterone (T). The potencies of the actual individual petrochemical agonists may, however, be relatively high, considering the complex composition of oils. Additive effects, antagonistic effects, and a synergistic effect were measured in the assays upon coexposure to a fixed concentration of standard (E2 or T) and increasing concentrations of oils. To investigate whether the observed effects were receptor-mediated, coexposures to the synthetic inhibitors ICI 182,780 (ERbeta assay) or flutamide (AR assay), a fixed concentration of standard, and various concentrations of oils were performed. The results suggested that the androgenic effects were receptor mediated, whereas the estrogenic effects may be only partially mediated via the receptor. The present study indicates that oils contain compounds with possible endocrine-disrupting potential, some of them acting via the hormone receptors.
Vrabie
Cozmina M
CM
Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands.
Candido
Angelica
A
van Duursen
Majorie B M
MB
Jonker
Michiel T O
MT
D000726:Androgen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000502:physiology*; D005485:Flutamide / Q000494:pharmacology; D010578:Petroleum / Q000633:toxicity*; D011944:Receptors, Androgen / Q000502:physiology*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
D000726:Androgen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010578:Petroleum; D011944:Receptors, Androgen; D005485:Flutamide