The 4-hydroxyestrone: Electron emission, formation of secondary metabolites and mechanisms of carcinogenesis

Abstract

Abstract4-Hydroxyestrone (4-OHE 1 ), a typical cancer-inducing metabolite, originating from 17β-estradiol (17β-E2), was chosen as a model for the studies. The aim was to get a deeper insight in the mechanisms of its ability to initiate cancer. It was found, that 4-OHE 1 can eject electrons , when excited in the singlet state by monochromatic UV-light (γ = 254 nm) in polar media (water:ethanol = 40:60 vol.%). The quantum yield , determined for various 4-OHE 1 concentrations, is found to be as high as that previously observed for 17β-E2. It decreases with increasing substrate concentration, but it is enhanced at higher temperature. The ability of 4-OHE 1 to eject as well as to consume and to transfer electrons to other biological systems, classifies it as an electron mediator, similar to 17β-E2.The 4-OHE 1 transients resulting of the electron emission process are leading to the formation of secondary metabolites. Surprisingly, it was established that the secondary metabolites possess likewise the ability to eject as well as to consume electrons. Hence, they behave similar like 17β-E2. However, the structure of the secondary formed metabolites, which determinates their biological properties and carcinogenity, depends on the nature of the available reaction partners involved in their formation. A probable reaction mechanism explaining the subject matter is discussed.

Electron emission and product analysis of estrone: progesterone interactions studied by experimentsin vitro

“…As reported in previous studies [1][2][3][4], the Q(e aq − ) yields decrease with increasing substrate concentration as a consequence of the associate formation. As already mentioned, these unstable complexes are supposed to consume a part of the emitted electrons.…”

“…Most likely, the electrons are emitted from the π-electron structure of ring A, as previously established with phenol and related compounds [20]. The process is illustrated in Equation (4): (4) The observed pH-decrease (inset II in Figures 1 and 2) supports the existence of reaction (4) by the formation of H + anions.…”

“…The same capability was also observed for other hormones like the phytohormone genistein [3], 4-hydroxyestrone (4-OHE1) [4], adrenaline (ADR) [5], etc. Thereby, a part of the ejected electrons are consumed by the hormones themselves with the reaction rate constant of k(e aq The transients resulting of the electron ejection process of the sexual hormones may interact with substances that are present in the actual media and form certain metabolites.…”

Hormones: electron emission, communication, mutual interaction, regeneration, metabolites, carcinogenesis and receptor action

“…Representatives of this hormone group were reported: 17 β -estradiol (17 β E2) [8,10] , estrone (E1) [15] and 4-hydroxyestrone (4-HOE1) [16] . The observed yield of the ejected e aq − from their singlet excited state was higher compared to other hormone types, which will be discussed subsequently.…”

“…The observed effect, which could be shown for all tested hormones, is based on the self-consumption of e aq − in competition with the rate of e aq − emission. Obviously, the reaction mechanisms involved are rather Table 4 Q(e aq − )-yields obtained at various 4-hydroxy-estrone (4-OHE1) concentrations at 37 ° C and 45 ° C by UV-excitation (253 nm; pH 7.4); peak (A) shows the e aq − -yield derived from original molecules, (B) form primary products and (C) from secondary products [16] . a UV-irradiation at 45 ° C .…”