Abstract: The homeodomain transcription factors PHOX2A and PHOX2B are vital for development of the autonomic nervous system. Their spatial and temporal expression at the neural crest is instrumental in determining neuronal precursor fate, and by regulating DbetaH expression, the enzyme catalysing noradrenaline synthesis from dopamine, they also play a role in determination of noradrenergic phenotype. Disturbing this finely regulated process leads to disruption of autonomic development and autonomic dysfunction syndromes such as DbetaH deficiency. As it had previously been shown that the catecholamine system is responsive to ELF-EMF, and as this has also been linked to various pathologies and to certain types of cancer, we wondered whether exposure to this type of radiation could affect the expression of PHOX2A, PHOX2B and DbetaH, also during differentiation triggered by retinoic acid. To investigate this possibility we exposed the human SH-SY5Y neuroblastoma cell line to 50 Hz power-line magnetic field at various flux densities and for various exposure times. We measured gene expression in exposed cells compared to control cells and also investigated any changes at protein level. Using our exposure protocol, we found no changes at either transcript or protein level of these important components of the autonomic nervous system and catecholaminergic system.

Abstract: We present possibilities and trends of ELF bioelectromagnetic effects in the mT amplitude range on cancer cells and on mice bearing tumors. In contrast to invasive electrochemotherapy and electrogenetherapy, using mostly needle electrodes and single high-amplitude electropulses for treatment, extremely low-frequency (ELF) pulsating electromagnetic fields (PEMF) and sinusoidal electromagnetic fields (SEMF) induce tumor cell apoptosis, inhibit angiogenesis, impede proliferation of neoplastic cells, and cause necrosis non invasively, whereas human lymphocytes are negligibly affected. Our successful results in killing cancer cells-analyzed by trypan blue staining or by flow cytometry-and of the inhibition of MX-1 tumors in mice by 15-20 mT, 50 Hz treatment in a solenoid coil also in the presence of bleomycin are presented in comparison to similar experimental results from the literature. In conclusion, the synergistic combinations of PEMF or SEMF with hyperthermia (41.5 degrees C) and/or cancerostatic agents presented in the tables for cells and mice offer a basis for further development of an adjuvant treatment for patients suffering from malignant tumors and metastases pending the near-term development of suitable solenoids of 45-60 cm in diameter, producing >20 mT in their cores.

Abstract: Cryptochromes are flavoproteins that are evolutionary related to the DNA photolyases but lack DNA repair activity. Drosophila cryptochrome (dCRY) is a blue light photoreceptor that is involved in the synchronization of the circadian clock with the environmental light-dark cycle. Until now, spectroscopic and structural studies on this and other animal cryptochromes have largely been hampered by difficulties in their recombinant expression. We have therefore established an expression and purification scheme that enables us to purify mg amounts of monomeric dCRY from Sf21 insect cell cultures. Using UV-visible spectroscopy, mass spectrometry, and reversed phase high pressure liquid chromatography, we show that insect cell-purified dCRY contains flavin adenine dinucleotide in its oxidized state (FAD(ox)) and residual amounts of methenyltetrahydrofolate. Upon blue light irradiation, dCRY undergoes a reversible absorption change, which is assigned to the conversion of FAD(ox) to the red anionic FAD(.) radical. Our findings lead us to propose a novel photoreaction mechanism for dCRY, in which FAD(ox) corresponds to the ground state, whereas the FAD(.) radical represents the light-activated state that mediates resetting of the Drosophila circadian clock.