Johannes Hartmann

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

4-Hydroxyestrone (4-OHE(1)), a typical cancer-inducing metabolite, originating from 17beta-estradiol (17beta-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 (e(aq)(-)), when excited in the singlet state by monochromatic UV-light (lambda=254 nm) in polar media (water:ethanol=40:60 vol.%). The quantum yield Q(e(aq)(-)), determined for various 4-OHE(1) concentrations, is found to be as high as that previously observed for 17beta-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 17beta-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 17beta-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.

Method for regeneration of hormones: 17β-estradiol, 21α-hydroxyprogesterone and corticosterone. A pathway for a possible medical application

Abstract The hormones 17β-estradiol (17βE2), 21α-hydroxyprogesterone (21α-HOPRG) and corticosterone (CORT) were used as representative models for the study. As a source for hormone excitation in singlet state serviced monochromatic UV-light (λ=254 nm), it was stated that the transients resulting by e–aq emission in air-free mixture water/ethanol 40/60, as long as they are in “status nascendi”, can be regenerated by electron transfer from a potent electron donor, e.g., vitamin C. The hormone regeneration (%) strongly depends, after all, on specific hormone molecular structure, concentration, temperature, etc. Because of the large heterogenic molecular structures, the substrates dissolved in the solvent mixture form “associates” (unstable complexes) in concentrations >109 mol/L hormone. The hormones eject, but they also consume e–aq with a rather high reaction rate constant (k≈109 up to 2×1010 L/mol.s), therefore, they act as “electron mediators”. It was also observed that the hormones by dissolution in aerated solvent mixture are sensitive towards oxygen. For an explanation of the results, probable reaction mechanisms are presented. The described method offers a new pathway and possibilities for application in medicine.

The effect of progesterone on the electron emission and degradation of testosterone.

Based on recent findings that hormones can emit electrons () from their excited singlet state in polar media, it was of importance to study a possible mutual interaction of progesterone (PRG) and testosterone (TES) in this respect. Hormones of highest purity were dissolved in an air-free mixture of 40% triply distilled water and 60% ethanol, because the hormones are unsoluble in water. As energy source for substrate excitation in singlet state served a monochromatic UV-light (254 nm), the emitted electrons were scavenged by chloroethanol, whereby the quantum yield of produced Cl− ions, Q (Cl−), is equal to Q(). Hormone degradation initiated by the electron emission was studied by HPLC method, using a Zorbax Eclipse XDB-C18 column (150 mm × 4.6 mm, 5 μm). The quantum yield of emitted , Q(), from TES was 3.6 times higher than that from PRG, which is explained by the different molecular structures of the hormones. Observed 2nd and 3rd maxima of electron emission indicate the ability of TES and PRG products to also eject , but with lower yield. It can be stated that a part of the emitted electrons from TES are consumed by PRG·+ leading to a partial regeneration of hormone. The present results offer a deeper insight in the biological behavior of hormones.