Henning Hintzsche

Micronucleus frequency in buccal mucosa cells of mobile phone users.

Mobile phones are being used extensively throughout the world, with more than four billion accounts existing in 2009. This technology applies electromagnetic radiation in the microwave range. Health effects of this radiation have been subject of debate for a long time, both within the scientific community and within the general public. This study investigated the effect of mobile phone use on genomic instability of the human oral cavitys mucosa cells. 131 Individuals donated buccal mucosa cells extracted by slightly scraping the oral cavity with a cotton swab. Every participant filled out a questionnaire about mobile phone use including duration of weekly use, overall period of exposure and headset usage. 13 Individuals did not use mobile phones at all, 85 reported using the mobile phone for three hours per week or less, and 33 reported use of more than three hours per week. Additionally, information on age, gender, body weight, smoking status, medication and nutrition was retrieved. For staining of the cells a procedure using alpha-tubulin-antibody and chromomycin A(3) was applied. Micronuclei and other markers were evaluated in 1000 cells per individual at the microscope. A second scorer counted another 1000 cells, resulting in 2000 analyzed cells per individual. Mobile phone use did not lead to a significantly increased frequency of micronuclei.

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G0/G1 phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.

Terahertz Radiation Induces Spindle Disturbances in Human-Hamster Hybrid Cells

Abstract The aim of this study was to investigate and quantify the production of spindle disturbances in AL cells, a human-hamster hybrid cell line, by 0.106 THz radiation (continuous wave). Monolayer cultures in petri dishes were exposed for 0.5 h to 0.106 THz radiation with power densities ranging from 0.043 mW/cm2 to 4.3 mW/cm2 or were kept under sham conditions (negative control) for the same period. As a positive control, 100 µg/ml of the insecticide trichlorfon, which is an aneuploidy-inducing agent, was used for an exposure period of 6 h. During exposure, the sample containers were kept at defined environmental conditions in a modified incubator as required by the cells. Based on a total of 6,365 analyzed mitotic cells, the results of two replicate experiments suggest that 0.106 THz radiation is a spindle-acting agent as predominately indicated by the appearance of spindle disturbances at the anaphase and telophase (especially lagging and non-disjunction of single chromosomes) of cell divisions. The findings in the present study do not necessarily imply disease or injury but may be important for evaluating possible underlying mechanisms.

Terahertz Electromagnetic Fields (0.106 THz) Do Not Induce Manifest Genomic Damage In Vitro

Terahertz electromagnetic fields are non-ionizing electromagnetic fields in the frequency range from 0.1 to 10 THz. Potential applications of these electromagnetic fields include the whole body scanners, which currently apply millimeter waves just below the terahertz range, but future scanners will use higher frequencies in the terahertz range. These and other applications will bring along human exposure to these fields. Up to now, only a limited number of investigations on biological effects of terahertz electromagnetic fields have been performed. Therefore, research is strongly needed to enable reliable risk assessment. Cells were exposed for 2 h, 8 h, and 24 h with different power intensities ranging from 0.04 mW/cm2 to 2 mW/cm2, representing levels below, at, and above current safety limits. Genomic damage on the chromosomal level was measured as micronucleus formation. DNA strand breaks and alkali-labile sites were quantified with the comet assay. No DNA strand breaks or alkali-labile sites were observed as a consequence of exposure to terahertz electromagnetic fields in the comet assay. The fields did not cause chromosomal damage in the form of micronucleus induction.

Terahertz Radiation at 0.380 THz and 2.520 THz Does Not Lead to DNA Damage in Skin Cells In Vitro

The question whether nonionizing electromagnetic radiation of low intensity can cause functional effects in biological systems has been a subject of debate for a long time. Whereas the majority of the studies have not demonstrated these effects, some aspects still remain unclear, e.g., whether high-frequency radiation in the terahertz range affects biological systems. In particular for frequencies higher than 0.150 THz, investigations of the ability of radiation to cause genomic damage have not been performed. In the present study, human skin cells were exposed in vitro to terahertz radiation at two specific frequencies: 0.380 and 2.520 THz. Power intensities ranged from 0.03–0.9 mW/cm2 and the cells were exposed for 2 and 8 h. Our goal was to investigate whether the irradiation induced genomic damage in the cells. Chromosomal damage was not detected in the different cell types after exposure to radiation of both frequencies. In addition, cell proliferation was quantified and found to be unaffected by the exposure, and there was no increase in DNA damage measured in the comet assay for both frequencies. For all end points, cells treated with chemicals were included as positive controls. These positive control cells clearly showed decreased proliferation and increased genomic damage. The results of the present study are in agreement with findings from other studies investigating DNA damage as a consequence of exposure to the lower frequency range (<0.150 THz) and demonstrate for the first time that at higher frequencies (0.380 and 2.520 THz), nonionizing radiation does not induce genomic damage.

Signaling steps in the induction of genomic damage by insulin in colon and kidney cells

Diabetes mellitus (DM), a disease with almost 350 million people affected worldwide, will be the seventh leading cause of death by 2030. Diabetic patients develop various types of complications, among them an increased rate of malignancies. Studies reported the strong correlation between DM and several cancer types, of which colon and kidney cancers are the most common. Hyperinsulinemia, the high insulin blood level characteristic of early diabetes type 2, was identified as a risk factor for cancer development. In previous studies, we showed that an elevated insulin level can induce oxidative stress, resulting in DNA damage in colon cells in vitro and in kidney cells in vitro and in vivo. In the present study, we elucidate the signaling pathway of insulin-mediated genotoxicity, which is effective through oxidative stress induction in colon and kidney. The signaling mechanism is starting by phosphorylation of the insulin and insulin-like growth factor-1 receptors, followed by activation of phosphatidylinositide 3-kinase (PI3K), which in turn activates AKT. Subsequently, mitochondria and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) isoforms (Nox1 and Nox4 in colon and kidney, respectively) are activated for reactive oxygen species (ROS) production, and the resulting excess ROS can attack the DNA, causing DNA oxidation. We conclude that hyperinsulinemia represents an important risk factor for cancer initiation or progression as well as a target for cancer prevention in diabetic patients.

Effects of Terahertz Radiation on Biological Systems

Effects of electromagnetic fields on biological systems of all levels, ranging from isolated biomolecules to whole organisms, have been investigated comprehensively for a long time. Due to a lack of suitable sources and detectors, the terahertz frequency range has not been investigated to the same amount as other frequencies. Even though early reports date back to the 1960s, thorough research has only been conducted during the last decade. The aim of this review is to give a summary of all available publications on this topic. A comprehensive literature research was conducted resulting in 37 identified publications. An overview of publication analysis is presented, followed by a detailed description of theoretical investigations. Subsequently all experimental investigations are described, including details on frequency, exposure time, power density, biological system, and outcome of the studies.

Field Exposure and Dosimetry in the THz Frequency Range

With a growing number of applications utilizing THz radiation appearing on the market the question of health protection against non-ionizing electromagnetic fields arises in this frequency range, as at lower frequencies before. To date, about 50 independent empirical studies on living organisms, model systems and cells have been performed to clarify bio-electromagnetic interaction in the THz frequency range. Many of these studies find behavioral effects or effects on the cellular level, even at non-thermal exposure levels, while others do not report effects other than thermally induced damage. We discuss the general challenges in performing reliable field exposure experiments in the THz frequency range and describe a methodology that was adopted in a large campaign searching for genotoxic effects of THz radiation in vitro.

Fate of micronuclei and micronucleated cells

The present review describes available evidence about the fate of micronuclei and micronucleated cells. Micronuclei are small, extranuclear chromatin bodies surrounded by a nuclear envelope. The mechanisms underlying the formation of micronuclei are well understood but not much is known about the potential fate of micronuclei and micronucleated cells. Many studies with different experimental approaches addressed the various aspects of the post-mitotic fate of micronuclei and micronucleated cells. These studies are reviewed here considering four basic possibilities for potential fates of micronuclei: degradation of the micronucleus or the micronucleated cell, reincorporation into the main nucleus, extrusion from the cell, and persistence in the cytoplasm. Two additional fates need to be considered: premature chromosome condensation/chromothripsis and the elimination of micronucleated cells by apoptosis, yielding six potential fates for micronuclei and/or micronucleated cells. The available data is still limited, but it can be concluded that degradation and extrusion of micronuclei might occur in rare cases under specific conditions, reincorporation during the next mitosis occurs more frequently, and the majority of the micronuclei persist without alteration at least until the next mitosis, possibly much longer. Overall, the consequences of micronucleus formation on the cellular level are still far from clear, but they should be investigated further because micronucleus formation may contribute to the initial and later steps of malignant cell transformation, by causing gain or loss of genetic material in the daughter cells and by the possibility of massive chromosome rearrangement in chromosomes entrapped within a micronucleus by the mechanisms of chromothripsis and chromoanagenesis.

900 MHz radiation does not induce micronucleus formation in different cell types

The exposure of the population to non-ionising electromagnetic radiation is still increasing, mainly due to mobile communication. Whether low-intensity electromagnetic fields can cause other effects apart from heating has been a subject of debate. One of the effects, which were proposed to be caused by mobile phone radiation, is the occurrence of mitotic disturbances. The aim of this study was to investigate possible consequences of these mitotic disturbances as manifest genomic damage, i.e. micronucleus induction. Cells were irradiated at a frequency of 900 MHz, which is located in one of the main frequency bands applied for mobile communication. Two cell types were used, HaCaT cells as human cells and A(L) cells (human-hamster hybrid cells), in which mitotic disturbances had been reported to occur. After different post-exposure incubation periods, cells were fixed and micronucleus frequencies were evaluated. Both cell types did not show any genomic damage after exposure. To adapt the protocol for the micronucleus test into the direction of the protocol for mitotic disturbances, the post-exposure incubation period was reduced and exposure time was extended to one cell cycle length. This did not result in any increase of the genomic damage. In conclusion, micronucleus induction was not observed as a consequence of exposure to non-ionising radiation, even though this agent was reported to cause mitotic disturbances under similar experimental conditions.