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The influence of endocrine disruptors on biotransformation enzymes
Klusoňová, Zuzana ; Bořek Dohalská, Lucie (advisor) ; Linhartová, Lucie (referee)
Endocrine disruptors (ED) are compounds that interfere with the endocrine system by mimicking or antagonising the effects of endogenous hormones. The synthetic estrogen 17-ethinylestradiol (EE2), a major component of oral contraceptives and a human strong carcinogen benzoapyrene (BaP) are assigned as an exogenous ED whereas the natural estrogenic hormone 17-estradiol (E2) figures as an endogenic endocrine disruptor. In this thesis the rats were treated with these ED individually and in combination, and their effect was studied on the gene and protein expression of cytochrome P450 1A1, 2C11 and 2C6 in rat liver, lung and kidney. In addition, the effect of the mentioned ED and their combinations on CYP1A and CYP2C specific enzyme activity and on metabolism of 17-ethinylestradiol in rat liver microsomal samples was studied. Changes in CYP gene and protein expression were analyzed by real-time PCR and Western blotting, CYP specific activity and metabolism of EE2 were investigated by HPLC method. It has been confirmed that BaP acts as a strong inducer of CYP1A1 in rat liver, lung and kidney, whereas EE2 or E2 alone revealed no significant effect on the expression of this CYP. However, when EE2 or E2 were administered to rats together with BaP, they considerably decreased the BaP-mediated CYP1A1...
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The effect of selected endocrine disruptors on the cytochromes P450 1A1 and 2C
Klusoňová, Zuzana ; Bořek Dohalská, Lucie (advisor) ; Linhartová, Lucie (referee)
Many currently produced chemicals reveal specific properties which allow them to be referred to as endocrine disruptors (ED). These substances exhibit an exogenic hormone activity and usually act as antagonists or agonists of endogenic hormones. The exogenic EDs studied in this work were 17α-ethinylestradiol (EE2) and benzoapyrene (BaP). 17β-estradiol (E2), a typical endogenic hormone, was also included to the study. In the presented work, the effect of these EDs and their combinations on the expression and specific activities of cytochromes P450 (CYP) 1A1 and 2C was determined. First, the microsomal fraction (MF) of liver, kidney and lung of rats premedicated with these compounds or without premedication was isolated. CYP expression was assessed by the Western blot analyses in these MF samples. Moreover, CYP1A1 and CYP2C specific activities were evaluated. It was found that premedication of rats with BaP increased CYP1A1 expression in all above mentioned organs. Whereas BaP strongly induced rat CYP1A1, EE2 and E2 were almost without this effect. But, when these disruptors were administered to rats with BaP, they supported its potency to induce CYP1A1. Further, CYP2C11 expression and its specific activity were gently increased by premedication of rat with EE2 and its combination with BaP....
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