Synthesis and characterization of estrogen 2,3- and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus horseradish peroxidase-activated catechol estrogens.
Catechol estrogens (CE) are among the major metabolites of estrone (E1) and 17 beta-estradiol (E2). Oxidation of these metabolites to semiquinones and quinones could generate ultimate carcinogenic forms of E1 and E2. The 2,3- and 3,4-quinones of E1 and E2 were synthesized by MnO2 oxidation of the corresponding CE, following the method for synthesizing E1-3,4-quinone [Abul-Hajj (1984) J. Steroid Biochem. 21, 621-622]. Characterization of these compounds was accomplished by UV, nuclear magnetic resonance, and mass spectrometry. The relative stability of these compounds was determined in DMSO/H2O (2:1) at room temperature, and the 3,4-quinones were more stable than the 2,3-quinones. The four quinones directly reacted with calf thymus DNA to form DNA adducts analyzed by the 32P-postlabeling method. The adducts were compared to those formed when the corresponding CE were activated by horseradish peroxidase (HRP) to bind to DNA. The E1- and E2-2,3-quinones formed much higher levels of DNA adducts than the corresponding 3,4-quinones. In addition, many of the adducts (70-90%) formed by the E1- and E2-2,3-quinones appeared to be the same as those formed by activation of 2-OHE1 or 2-OHE2 by HRP to bind to DNA. Little overlap was observed between the adducts formed by E1- and E2-3,4-quinones and HRP-activated 4-OHE1 and 4-OHE2. These results suggest that semiquinones and/or quinones are ultimate reactive intermediates in the peroxidatic activation of catechol estrogens.
Dwivedy
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I
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Devanesan
P
P
Cremonesi
P
P
Rogan
E
E
Cavalieri
E
E
D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D004958:Estradiol / Q000737:chemistry; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000737:chemistry; D002393:Estrogens, Catechol / Q000138:chemical synthesis* / Q000737:chemistry; D004970:Estrone / Q000737:chemistry; D006735:Horseradish Peroxidase; D010084:Oxidation-Reduction; D010761:Phosphorus Radioisotopes; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D045166:Estradiol Congeners; D002393:Estrogens, Catechol; D010761:Phosphorus Radioisotopes; D011809:Quinones; D004970:Estrone; D004958:Estradiol; D004247:DNA; D006735:Horseradish Peroxidase