Free radical action on sexual hormones in respect to cancer

Taking into consideration the present state of the art in respect to the subject matter of the project, it appears that some metabolites of the sexual hormones, 17ß-estradiol (17ßE2), progesterone (PRG) and testosterone (T) can initiate cancer. Particularly, 17ßE2 and its metabolites, those originating from the A-ring of the molecule, have been subjected to the most studies with regard to breast cancer. PRG and T were relatively less investigated in this respect. In the case of PRG was found, that one of the three metabolites (5aP) exhibits metastatic properties, whereas the other two (3aHP and 20aHP) shows opposite action. The metabolites of T showed different action on various types of cancer cells used as a model for studies. However, one of them, 5a-dihydro-testosterone, is found to be involved into pathogenesis of human prostatic hyperplasma. It should be also mentioned, that very recently was established by our research group the ability of 17ßE2, PRG and T to emit electrons in polar media from their excited state. This fact has important biological consequences in respect to the formation of metabolites and carcinogenesis. Summing up, it can be stated, that up to now no studies have been undertaken to elucidate the effects initiated by the oxidizing (OH, O 2 - etc.) and reducing (e aq - , H, R etc.) free radicals, which are permanently generated and consumed in human organism. Since the human organism contains of about 70% water, one can produce each desired free radical by irradiation (Gamma-ray or high energy electrons) of aqueous solution or in mixtures of DMSO-water or alcohol-water mixtures in order to simulate the biological conditions. Based on the above mentioned facts the objectives of the present research project embrasses the following points: Experiments in vitro: - Suspensions of cancer cells and of bacteria (used as a model) in buffer only and in media saturated with appropriate gas (argon, N2 O or air) as well as in the presence of formiate, in order to achieve the action of desired kind of free radicals, will be irradiated as a function of absorbed radiation dose. (The radical concentration is proportional to the dose) - Similar experiments using each individual hormone in buffer will be performed under the same conditions as above indicated. - The same experimental conditions, but using cancer cells in presence of each individual hormone. - AMES-test: for examination the carcinogenity of the hormones and their metabolites. Chemical analysis of various systems, since the resulting hormone products play certain biological role Pulse radiolysis investigations The spectroscopic and kinetic characterisation of the transients resulting by the attack of e aq - , OH and O2 on the hormones will be performed by means of the pulse radiolysis method. These experiments will be performed in cooperation with Dr. Salvatore Silvano EMMI, Instituto ISOF-CNR, Bologna, Italy. The results will be published

Taking into consideration the present state of the art in respect to the subject matter of the project, it appears that some metabolites of the sexual hormones, 17ß-estradiol (17ßE2), progesterone (PRG) and testosterone (T) can initiate cancer. Particularly, 17ßE2 and its metabolites, those originating from the A-ring of the molecule, have been subjected to the most studies with regard to breast cancer. PRG and T were relatively less investigated in this respect. In the case of PRG was found, that one of the three metabolites (5aP) exhibits metastatic properties, whereas the other two (3aHP and 20aHP) shows opposite action. The metabolites of T showed different action on various types of cancer cells used as a model for studies. However, one of them, 5a-dihydro-testosterone, is found to be involved into pathogenesis of human prostatic hyperplasma. It should be also mentioned, that very recently was established by our research group the ability of 17ßE2, PRG and T to emit electrons in polar media from their excited state. This fact has important biological consequences in respect to the formation of metabolites and carcinogenesis. Summing up, it can be stated, that up to now no studies have been undertaken to elucidate the effects initiated by the oxidizing (OH, O 2 - etc.) and reducing (e aq - , H, R etc.) free radicals, which are permanently generated and consumed in human organism. Since the human organism contains of about 70% water, one can produce each desired free radical by irradiation (Gamma-ray or high energy electrons) of aqueous solution or in mixtures of DMSO-water or alcohol-water mixtures in order to simulate the biological conditions. Based on the above mentioned facts the objectives of the present research project embrasses the following points: Experiments in vitro: Suspensions of cancer cells and of bacteria (used as a model) in buffer only and in media saturated with appropriate gas (argon, N2 O or air) as well as in the presence of formiate, in order to achieve the action of desired kind of free radicals, will be irradiated as a function of absorbed radiation dose. (The radical concentration is proportional to the dose) Similar experiments using each individual hormone in buffer will be performed under the same conditions as above indicated. The same experimental conditions, but using cancer cells in presence of each individual hormone. AMES-test: for examination the carcinogenity of the hormones and their metabolites. Chemical analysis of various systems, since the resulting hormone products play certain biological role Pulse radiolysis investigations The spectroscopic and kinetic characterisation of the transients resulting by the attack of e aq - , OH and O2 - on the hormones will be performed by means of the pulse radiolysis method. These experiments will be performed in cooperation with Dr. Salvatore Silvano EMMI, Instituto ISOF-CNR, Bologna, Italy.