Initial studies of a phytoestrogen-deoxyribonucleic acid interaction

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 1; no. 5; pp. 377 - 387
• Main Authors: LEHNER, A. F, MULDOON, T. G, MAHESH, V. B, BRANSOME, E. D. JR, HENDRY, L. B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.05.1987
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Base Composition; Biological and medical sciences; Cattle; Coumarins; Coumestrol; DNA; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Kinetics; Models, Molecular; Nucleic Acid Conformation; Other biological molecules; Terpenes, steroids. Hormones; Thermodynamics; DNA; Estrogen; Plant origin; Fluorescence; Molecular interaction; Sex steroid hormone; Ultraviolet spectrometry
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/mend-1-5-377

Molecular modeling studies show that estrogens such as estradiol complement the topography of spaces between base pairs in unwound DNA and simultaneously hydrogen bond phosphate moieties on opposite strands. We demonstrate here that the phytoestrogen coumestrol has this capability, in addition to its documented properties of UV absorbance at lambda greater than 300 nm and fluorescence. The latter properties enable spectroscopic examination of interactions with DNA by methods not possible with estrogenic steroids. On exposure to calf thymus DNA, the UV spectrum of coumestrol displays a bathochromic shift and simultaneous hypochromic effect with an isosbestic point at 370 nm, suggesting a shift between coexisting free and bound states. Similar results are observed with the intercalating agents adriamycin, ethidium bromide, and acridine. The fluorescence spectrum of coumestrol is quenched on exposure to DNA as are those of adriamycin and acridine. Coumestrol differs from the intercalators in that denatured DNA does not affect its UV spectrum or alter its relative fluorescence yield. Unlike classical intercalators, coumestrol has no influence on the thermal stability of calf thymus DNA. Preliminary electrophoretic analysis of DNA plasmid conformers indicates that coumestrol is incapable of significantly altering DNA superhelical density, in contrast to ethidium bromide. These initial physicochemical data provide evidence for the DNA base-estrogen electronic and/or hydrophobic interactions suggested by modeling studies, yet tend to rule out classical intercalation as an explanation for these phenomena.