New methods for detection of potential endocrine disruptors.
It has been hypothesized that recent adverse trends in humans are linked to an increased exposure to potential endocrine disrupting agents. These include widely used compounds that mimic the action of sex hormones, including bisphenol A, phthalates and parabens. Since the chemical structure is not sufficient to determine whether a chemical will act as an oestrogen, there is a need for assays that can determine whether a compound interferes with the endocrine systems. The Environmental Protection Agency has recently suggested a testing scheme, composed of an initial screening followed by a more comprehensive investigation of chemicals that are positive in the screening. The screening will use several short-term assays to screen many thousands of compounds for potential endocrine disrupting properties. However, none of these tests determines compound-induced effects on the expression of endogenous genes, which is the cause of the adverse effects. We propose to use a precise quantification of the expression levels of endogenous oestrogen-regulated genes to test whether a chemical has oestrogenic properties, and describe how an endogenous gene expression assay can be established and conducted. Furthermore, different applications of such an assay are discussed: in cell cultures; in experimental animals; or, optimally, directly in blood samples from exposed humans.
Kledal
T J
TJ
Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Jorgensen
M
M
Mengarda
F
F
Skakkebaek
N E
NE
Leffers
H
H
D000818:Animals; D001185:Artificial Intelligence; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004702:Endocrine Glands / Q000187:drug effects*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D005821:Genetic Techniques; D005820:Genetic Testing; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D014481:United States; D014484:United States Environmental Protection Agency
D017931:DNA Primers; D004968:Estrogens, Non-Steroidal; D005819:Genetic Markers