The origin of cancer still remains one of the astonishing scientific mysteries. Certain types of breast cancers underline a definite impact of hormones in carcinogenesis. Thereby, much effort has been spent on the elucidation of the generation and metabolism of steroid hormones and their degradation in peripheral target tissues like the female breast. Free radicals are generated permanently in the human organism. These short-living species are known to influence the metabolism of estrogens and even might induce damages in the DNA. It has been previously found that various biological compounds and hormones can eject solvated electrons (eaq-) when being excited in their singlet state in a polar media of a water-ethanol (EtOH) mixture. Actual studies with estrogens showed that the electron emission mostly takes place at the pi-electron structure of the A-ring and is followed by an intramolecular electron transfer from the OH-group to the ring resulting in a phenoxyl-radical transient (O2*-, OH*-) having several mesomere structures. Each of these radical structures can lead to the formation of metabolites with specific biological properties. Based on these observations, it was of interest to determine the eaq- originating from the estrogen estrone (E1) and vitamin C (VitC) and to examine the fate of the resulting transients of E1. The quanta yields of eaq-, Q(eaq-), of E1 and VitC were calculated and compared. Analyses with HPLC were performed in order to investigate the degradation of E1 and VitC, to observe a possible regeneration of E1 by an electron transfer of VitC and to determine degradation products of the substances. The results of these investigations enabled the corroboration of a hypothetic biochemical behavior of the substances in regard to carcinogenesis. Moreover, experiments in vitro with MCF-7 breast cancer cells and E.coli bacteria were carried out. The cells and bacteria were incubated in E1, PRG and VitC separately and in mixtures under the influence of [gamma]-ray to study the impact of oxidizing and reducing free radicals on the cells and bacteria and to investigate the impact on estrone (E1) in the absence and presence of the antioxidant vitamin C (VitC) acting as a potent electron donor. The results were compared in order to demonstrate the influence of PRG and Vit C on the biological behaviour of E1 and to elucidate the role of radicals and hormones in the initiation of cancer and to find possible approaches for the treatment of cancer.
The results showed that E1 and VitC are both potent donors for electrons. The yield of electrons depends on the concentration of the substrate, on the pH in the media and on temperature. A delayed degradation and a partly regeneration of E1 by the electron transfer ejected from VitC was observed and confirmed by HPLC-analyses. The VitC-induced regeneration of E1 could hypothetically result in a delayed formation of E1-radicals and potential carcinogenic metabolites. It was confirmed that the functional -OH group at the A-ring of the E1-molecule plays a decisive part in the biochemical behaviour of E1 in the human organism due to its mesomere structures and the resulting various types of radicals. In vitro experiments with MCF-7 cells showed an antiproliferative impact of E1 which was pronounced when incubating the cells in a mix of E1 and PRG. In experiments with E.coli, an antiproliferative action of VitC was found in an aerated media. The present work focuses on hypothetical biological pathways in the metabolism of the estrogen E1. Different possible reaction mechanisms are discussed and offer new approaches in understanding the role of E1 as a potential radical inducer in the human organism. The obtained results could contribute precious approaches for the therapeutic application of estrogens and could make a simultaneous substitution of VitC conceivable.