Abstract
In a previous study, we found a dose-dependent synergistic effect in recombinant yeast stably transfected with the human androgen receptor (AR), in response to co-exposure to testosterone and a commercially-available lubricant (engine) oil for cars. As there is relatively little knowledge on synergistic toxic effects and causative compounds, particularly for the androgenic system, the objective of the present study was to investigate this oil in more detail. The oil was fractionated into SARA fractions (so-called 'saturates', 'aromatics', 'resins', and 'asphaltenes') by open column chromatography. Surprisingly, when exposing the recombinant AR yeast to testosterone in combination with the separate SARA fractions, the synergistic effect could not be reproduced fully. After pooling the fractions again however, the full synergism returned. From subsequent exposures to combinations of two or three SARA fractions, it appeared that both the 'saturates' and the 'resins' fraction were required for obtaining the synergistic response with testosterone. This clearly demonstrates a synergistic effect related to the androgenic system caused by the joint action of at least three chemically-distinct compounds, or groups of compounds (i.e. testosterone, 'resins' and 'saturates'). Although detailed chemical analyses could not reveal the identity of the causative compounds and the in vivo relevance of the present results remains unclear, the results do add to the growing body of evidence on the potentially extremely complex character of mixture effects.
DOI
10.1016/j.chemosphere.2015.09.094
Publication Date
2015-10-23
Publication Title
Chemosphere
Volume
144
ISSN
0045-6535
Embargo Period
2016-10-24
Organisational Unit
Faculty of Science and Engineering
Keywords
Androgen receptor, Mixture toxicity, Petroleum, SARA, Synergism, Yeast
First Page
1142
Last Page
1147
Recommended Citation
Jonker, M. T., Candido, A., Vrabie, C., Scarlett, A., & Rowland, S. (2015) 'Synergistic androgenic effect of a petroleum product caused by the joint action of at least three different types of compounds', Chemosphere, 144, pp. 1142-1147. Available at: https://doi.org/10.1016/j.chemosphere.2015.09.094