scholarly journals Report of Partial Findings from the National Toxicology Program Carcinogenesis Studies of Cell Phone Radiofrequency Radiation in Hsd: Sprague Dawley® Sd Rats (Whole Body Exposure)

2016 ◽  
Author(s):  
Michael Wyde ◽  
Mark Cesta ◽  
Chad Blystone ◽  
Susan Elmore ◽  
Paul Foster ◽  
...  

AbstractThe U.S. National Toxicology Program (NTP) has carried out extensive rodent toxicology and carcinogenesis studies of radiofrequency radiation (RFR) at frequencies and modulations used in the U.S. telecommunications industry. This report presents partial findings from these studies. The occurrences of two tumor types in male Harlan Sprague Dawley rats exposed to RFR, malignant gliomas in the brain and schwannomas of the heart, were considered of particular interest and are the subject of this report. The findings in this report were reviewed by expert peer reviewers selected by the NTP and National Institutes of Health (NIH). These reviews and responses to comments are included as appendices to this report, and revisions to the current document have incorporated and addressed these comments. When the studies are completed, they will undergo additional peer review before publication in full as part of the NTP's Toxicology and Carcinogenesis Technical Reports Series. No portion of this work has been submitted for publication in a scientific journal. Supplemental information in the form of four additional manuscripts has or will soon be submitted for publication. These manuscripts describe in detail the designs and performance of the RFR exposure system, the dosimetry of RFR exposures in rats and mice, the results to a series of pilot studies establishing the ability of the animals to thermoregulate during RFR exposures, and studies of DNA damage. (1) Capstick M, Kuster N, Kuhn S, Berdinas-Torres V, Wilson P, Ladbury J, Koepke G, McCormick D, Gauger J, and Melnick R. A radio frequency radiation reverberation chamber exposure system for rodents; (2) Yijian G, Capstick M, McCormick D, Gauger J, Horn T, Wilson P, Melnick RL, and Kuster N. Life time dosimetric assessment for mice and rats exposed to cell phone radiation; (3) Wyde ME, Horn TL, Capstick M, Ladbury J, Koepke G, Wilson P, Stout MD, Kuster N, Melnick R, Bucher JR, and McCormick D. Pilot studies of the National Toxicology Program’s cell phone radiofrequency radiation reverberation chamber exposure system; (4) Smith-Roe SL, Wyde ME, Stout MD, Winters J, Hobbs CA, Shepard KG, Green A, Kissling GE, Tice RR, Bucher JR, and Witt KL. Evaluation of the genotoxicity of cell phone radiofrequency radiation in male and female rats and mice following subchronic exposure.SUMMARYThe purpose of this communication is to report partial findings from a series of radiofrequency radiation (RFR) cancer studies in rats performed under the auspices of the U.S. National Toxicology Program (NTP).1 This report contains peer-reviewed, neoplastic and hyperplastic findings only in the brain and heart of Hsd:Sprague Dawley® SD® (HSD) rats exposed to RFR starting in utero and continuing throughout their lifetimes. These studies found low incidences of malignant gliomas in the brain and schwannomas in the heart of male rats exposed to RFR of the two types [Code Division Multiple Access (CDMA) and Global System for Mobile Communications (GSM)] currently used in U.S. wireless networks. Potentially preneoplastic lesions were also observed in the brain and heart of male rats exposed to RFR.The review of partial study data in this report has been prompted by several factors. Given the widespread global usage of mobile communications among users of all ages, even a very small increase in the incidence of disease resulting from exposure to RFR could have broad implications for public health. There is a high level of public and media interest regarding the safety of cell phone RFR and the specific results of these NTP studies. Lastly, the tumors in the brain and heart observed at low incidence in male rats exposed to GSM-and CDMA-modulated cell phone RFR in this study are of a type similar to tumors observed in some epidemiology studies of cell phone use. These findings appear to support the International Agency for Research on Cancer (IARC) conclusions regarding the possible carcinogenic potential of RFR.2It is important to note that this document reviews only the findings from the brain and heart and is not a complete report of all findings from the NTP’s studies. Additional data from these studies in Hsd:Sprague Dawley® SD® (Harlan) rats and similar studies conducted in B6C3F1/N mice are currently under evaluation and will be reported together with the current findings in two forthcoming NTP Technical Reports.

2021 ◽  
Vol 24 ◽  
pp. 267-276
Author(s):  
Samantha McClenahan ◽  
Melinda Gunnell ◽  
Michael Owens

PURPOSE: α-Pyrrolidinovalerophenone (α-PVP) is a second-generation synthetic cathinone which acts as an inhibitor at the dopamine and norepinephrine transporters in the brain. These novel studies determined the pharmacokinetics (PK) of α-PVP in rats and then evaluated the effects of an α-PVP vaccine on the PK profile. METHODS: Adult male Sprague-Dawley rats were randomly divided into treatment groups (n = 24/group) in which the vaccinated rats received an initial and two booster immunizations of the α-PVP vaccine at 0, 3, and 9 wks. Control rats received saline injections. α-PVP (0.56, 1, 3 mg/kg, sc) was then administered to both groups between 11-12 weeks and serum samples were collected for determination of α-PVP serum concentrations by LC-MS/MS (n=6 rats/treatment/time). At 13 weeks, brain, heart and kidney concentrations of α-PVP were determined by LC-MS/MS after administration of 1 mg/kg α-PVP (n=4-5 rats/treatment/time). RESULTS: PK values in control rats showed dose-dependent increases in maximum serum concentrations (Cmax) and area under the curve (AUCinf) values with an elimination half-life (t1/2) of approximately 2.1 h. α-PVP exhibited linear PK profile in control rats. Vaccinated rats had significantly (p<0.05) higher serum Cmax and AUCinf values than controls, and significantly reduced total body clearance, volume of distribution and t1/2 values. Vaccinated rats had significantly lower α-PVP concentrations in the brain, heart, and kidney in comparison to control rats at early time points. CONCLUSION: Vaccination with the novel α-PVP vaccine significantly altered serum PK leading to a time-dependent reduction in brain, kidney and heart concentrations of α-PVP compared to controls.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.


2020 ◽  
Vol 318 (3) ◽  
pp. R634-R648 ◽  
Author(s):  
Zhigang Shi ◽  
Ding Zhao ◽  
Priscila A. Cassaglia ◽  
Virginia L. Brooks

In males, obesity increases sympathetic nerve activity (SNA), but the mechanisms are unclear. Here, we investigate insulin, via an action in the arcuate nucleus (ArcN), and downstream neuropathways, including melanocortin receptor 3/4 (MC3/4R) in the hypothalamic paraventricular nucleus (PVN) and dorsal medial hypothalamus (DMH). We studied conscious and α-chloralose-anesthetized Sprague-Dawley rats fed a high-fat diet, which causes obesity prone (OP) rats to accrue excess fat and obesity-resistant (OR) rats to maintain fat content, similar to rats fed a standard control (CON) diet. Nonspecific blockade of the ArcN with muscimol and specific blockade of ArcN insulin receptors (InsR) decreased lumbar SNA (LSNA), heart rate (HR), and mean arterial pressure (MAP) in OP, but not OR or CON, rats, indicating that insulin supports LSNA in obese males. In conscious rats, intracerebroventricular infusion of insulin increased MAP only in OP rats and also improved HR baroreflex function from subnormal to supranormal. The brain sensitization to insulin may elucidate how insulin can drive central SNA pathways when transport of insulin across the blood-brain barrier may be impaired. Blockade of PVN, but not DMH, MC3/4R with SHU9119 decreased LSNA, HR, and, MAP in OP, but not OR or CON, rats. Interestingly, nanoinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased LSNA only in OP rats, similar to PVN MTII-induced increases in LSNA in CON rats after blockade of sympathoinhibitory neuropeptide Y Y1 receptors. ArcN InsR expression was not increased in OP rats. Collectively, these data indicate that obesity increases SNA, in part via increased InsR signaling and downstream PVN MC3/4R.


2021 ◽  
Author(s):  
Ben-zhen Chen ◽  
Li-hua Jiang ◽  
Ming-qiang Zhang ◽  
Ling Tan ◽  
Wen-qin Zhou ◽  
...  

Abstract Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 hours on postnatal days (P) 5, 6, 7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, 26, 27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.


Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 126
Author(s):  
Alessandro Virtuoso ◽  
Pernille Tveden-Nyborg ◽  
Anne Marie Voigt Schou-Pedersen ◽  
Jens Lykkesfeldt ◽  
Heidi Kaastrup Müller ◽  
...  

Findings of the effect of high-fat feeding including “Cafeteria Diets” (CAF) on brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and prefrontal cortex (PFC) in rodents are conflicting. CAF is a non-standardized, highly palatable energy-rich diet composed by everyday food items for human consumption and is known to induce metabolic syndrome and obesity in rats. However, the highly palatable nature of CAF may counteract a negative effect of chronic stress on anticipatory behavior and synaptic plasticity in the hippocampus, hence represent a confounding factor (e.g., when evaluating functional effects on the brain). This study investigated the effects of a chronic, restricted access to CAF on BDNF, monoamine neurotransmitters, and redox imbalance in HIP and PFC in male rats. Our results show that CAF induced BDNF and its receptor TrkB in PFC compared to the controls (p < 0.0005). No differences in monoamine neurotransmitters were detected in either PFC or HIP. CAF increased dehydroascorbic acid and decreased malondialdehyde in PFC (p < 0.05), suggesting an early redox imbalance insufficient to induce lipid peroxidation. This study supports that a chronic CAF on a restricted schedule increases BDNF levels in the PFC of rats, highlighting that this may be a suboptimal feeding regime when investigating the effects of diet-induced obesity in the brain and emphasizing this as a point of attention when comparing the findings.


Author(s):  
Arnold Gutierrez ◽  
Kevin M. Creehan ◽  
Michael A. Taffe

AbstractBackgroundThe ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy. Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established.MethodWe adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.ResultsInhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups.ConclusionsThis work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ∼50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2069-2069
Author(s):  
Birgit Agerholm-Larsen ◽  
Helle K. Iversen ◽  
Jakob M. Moller ◽  
Per Ibsen ◽  
Kurt S. Jensen ◽  
...  

2069 Background: Electrochemotherapy (ECT) describes enhanced chemotherapeutic drug uptake after cell membranes have been made transiently permeable due to application of an electric field to the tumor. ECT is routinely used to treat skin metastases, with high response rates after once-only treatment. We have developed an electrode for use in the brain, both a rodent model and an electrode for clinical use. The aim of the present study was to evaluate ECT using intravenous (iv) bleomycin in a rat brain tumor model. Methods: Sprague Dawley male rats (7-11 week old) were inoculated with rat glial cell derived tumor cells (N32) through a burr hole in the skull. When tumors appeared on MRI, animals were allocated to ECT (iv bleomycin and local electric pulses), iv bleomycin only, iv bleomycin with placement of electrodes (no pulses), or no treatment. Bleomycin was injected iv in the tail vein (600µL, 3 IU/µL) and electrode deployment was made through the burr hole into the brain tissue. Electrochemotherapy parameters were 32 pulses, 100V, 100µs, 1Hz. Tumor size was determined based on contrast enhanced area from MR scans. Kaplan-Meyer events were defined as termination due to extensive tumor progression prior to end of the three independent experiments performed. Immuno-histo-pathology was performed after termination to verify MRI findings. Results: In 88% of the animals (14 of 16) treated with electrochemotherapy we found complete response (no tumor), validated by MRI and immuno-histo-pathology, whereas bleomycin only, bleomycin and electrodes, and no treatment showed progression in 11 out of 13 control animals. A Kaplan-Meier plot showed a pronounced improved survival for the ECT group as compared to controls within 3 weeks from treatment (p<0.001). Treatment was well tolerated. Conclusions: The present data suggest that electrochemotherapy with iv injection of bleomycin is a new promising treatment for brain tumors. In a clinical study using iv bleomycin and electrochemotherapy for brain metastases ( www.clinicaltrials.gov , ID:NCT01322100) the first patient has just been treated successfully with ECT, indicating feasibility of the approach in the clinical setting.


2019 ◽  
Vol 10 (4) ◽  
pp. 3554-3559
Author(s):  
Nuha Sh. Ali ◽  
Haidar Alsaedi

There is tremendous concern about the potential harmful effects of cell phone microwaves. The results are contradictory. However, the effects of these waves on the body have been reported. In this study, the effect of cellular microwaves on sperm parameters and total antioxidant capacity in relation to the duration of exposure and frequency of these waves were studied. This experimental study was conducted on male Sprague Dawley rats (150-200 g). The animals were randomly assigned to three groups (n = 18). Group 1 Natural control rat were fed to standard laboratory feeding Animals for 14 days. Group 2 animals were exposed to cell phone receiver stimulated waves (915 MHz frequency) for 14 days, and Group 3 animals were exposed to simulated waves of a cell phone antenna (950 MHz frequency) for 14 days. The results indicated that the total antioxidant capacity in all exposure groups decreased significantly compared with the control group (P <0.05). Increased exposure time within two weeks caused a statistically significant decrease in sperm motility and mobility (P <0.05).Effect of phone waves on liver and kidney of male Sprague Dawley rat. The study of pathological anatomy revealed a clear and appropriate deviation. These results found blood enzymes such as amino-aspartase transferase (AST), amino amines (ALT), and creatinine levels. The results showed no significant changes in both liver and kidney physiological functions. Malondialdehyde level (MDA) and total antioxidant contents were performed. The level of glutathione (GST), superoxide dismutase (SOD) was in normal ranges. Exposure to cell phone waves can reduce sperm movement and mobility in rats. These waves can also reduce the total antioxidant capacity in rats and lead to oxidative stress.


2021 ◽  
Author(s):  
Ben-zhen Chen ◽  
Li-hua Jiang ◽  
Ming-qiang Zhang ◽  
Wen-qin Zhou ◽  
Yu-chao Shang ◽  
...  

Abstract Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 hours on postnatal days (P) 5, 6, 7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, 26, 27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.


2006 ◽  
Vol 22 (5) ◽  
pp. 211-216 ◽  
Author(s):  
Halis Köylü ◽  
Hakan Mollaoglu ◽  
Fehmi Ozguner ◽  
Mustafa Nazýroölu ◽  
Namýk Delibap

Microwaves (MW) from cellular phones may affect biological systems by increasing free radicals, which may enhance lipid peroxidation levels of the brain, thus leading to oxidative damage. Melatonin is synthesized in and secreted by the pineal gland at night and exhibits anti-oxidant properties. Several studies suggest that supplementation with anti-oxidant can influence MW-induced brain damage. The present study was designed to determine the effects of MW on the brain lipid peroxidation system, and the possible protective effects of melatonin on brain degeneration induced by MW. Twenty-eight Sprague-Dawley male rats were randomly divided into three groups as follows: (1) sham-operated control group (N-8); (2) study 900-MHz MW-exposed group (N-8); and (3) 900-MHz MW-exposed-melatonin (100 mg/kg sc before daily MW exposure treated group) (N-10). Cortex brain and hippocampus tissues were removed to study the levels of lipid peroxidation as malonyl dialdehyde. The levels of lipid peroxidation in the brain cortex and hippocampus increased in the MW group compared with the control group, although the levels in the hippocampus were decreased by MW-melatonin administration. The brain cortex lipid peroxidation levels were unaffected by melatonin treatment. We conclude that melatonin may prevent MW-induced oxidative changes in the hippocampus by strengthening the anti-oxidant defense system, by reducing oxidative stress products.


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