Effects of mobile phone radiofrequency on the structure and function of the normal human hemoglobin

Widespread use of mobile phones has increased the human exposure to electromagnetic fields (EMFs). It is required to investigate the effect of EMFs on the biological systems. In this paper the effect of mobile phone RF (910 MHz and 940 MHz) on structure and function of HbA was investigated. Oxygen affinity was measured by sodium dithionite with UV–vis spectrophotometer. Structural changes were studied by circular dichroism and fluorescence spectroscopy. The results indicated that mobile phone EMFs altered oxygen affinity and tertiary structure of HbA. Furthermore, the decrease of oxygen affinity of HbA corresponded to the EMFs intensity and time of exposure.     

Exposure to 900 MHz electromagnetic field induces an unbalance between pro-apoptotic and pro-survival signals in T-lymphoblastoid leukemia CCRF-CEM cells

It has been recently established that low-frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high-frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low- and high-frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high-frequency EMFs could affect in vitro cell survival, we cultured acute T-lymphoblastoid leukemia cells (CCRF-CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high-frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro-apoptotic and pro-survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2-12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53-dependent and -independent apoptotic pathways while longer continuous exposure (24-48 h) determined silencing of pro-apoptotic signals and activation of genes involved in both intracellular (Bcl-2) and extracellular (Ras and Akt1) pro-survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self-defense response triggered by DNA damage, could confer to the survivor CCRF-CEM cells a further advantage to survive and proliferate.     

Influence of electromagnetic fields emitted by GSM-900 cellular telephones on the circadian patterns of gonadal, adrenal and pituitary hormones in men

The potential health risks of radiofrequency electromagnetic fields (RF EMFs) emitted by mobile phones are currently of considerable public interest. The present study investigated the effect of exposure to 900 MHz GSM radiofrequency radiation on steroid (cortisol and testosterone) and pituitary (thyroid-stimulating hormone, growth hormone, prolactin and adrenocorticotropin) hormone levels in 20 healthy male volunteers. Each subject was exposed to RF EMFs through the use of a cellular phone for 2 h/day, 5 days/ week, for 4 weeks. Blood samples were collected hourly during the night and every 3 h during the day. Four sampling sessions were performed at 15-day intervals: before the beginning of the exposure period, at the middle and the end of the exposure period, and 15 days later. Parameters evaluated included the maximum serum concentration, the time of this maximum, and the area under the curve for hormone circadian patterns. Each individual's pre-exposure hormone concentration was used as his control. All hormone concentrations remained within normal physiological ranges. The circadian profiles of prolactin, thyroid-stimulating hormone, adrenocorticotropin and testosterone were not disrupted by RF EMFs emitted by mobile phones. For growth hormone and cortisol, there were significant decreases of about 28% and 12%, respectively, in the maximum levels when comparing the 2-week (for growth hormone and cortisol) and 4-week (for growth hormone) exposure periods to the pre-exposure period, but no difference persisted in the postexposure period. Our data show that the 900 MHz EMF exposure, at least under our experimental conditions, does not appear to affect endocrine functions in men.     

Exposure to 900 MHz electromagnetic field induces an unbalance between pro‐apoptotic and pro‐survival signals in T‐lymphoblastoid leukemia CCRF‐CEM cells

The original article to which this Erratum was published in J. Cell. Physiol. 198:324–332, 2004 It has been recently established that low‐frequency electromagnetic field (EMFs) exposure induces biological changes and could be associated with increased incidence of cancer, while the issue remains unresolved as to whether high‐frequency EMFs can have hazardous effect on health. Epidemiological studies on association between childhood cancers, particularly leukemia and brain cancer, and exposure to low‐ and high‐frequency EMF suggested an etiological role of EMFs in inducing adverse health effects. To investigate whether exposure to high‐frequency EMFs could affect in vitro cell survival, we cultured acute T‐lymphoblastoid leukemia cells (CCRF‐CEM) in the presence of unmodulated 900 MHz EMF, generated by a transverse electromagnetic (TEM) cell, at various exposure times. We evaluated the effects of high‐frequency EMF on cell growth rate and apoptosis induction, by cell viability (MTT) test, FACS analysis and DNA ladder, and we investigated pro‐apoptotic and pro‐survival signaling pathways possibly involved as a function of exposure time by Western blot analysis. At short exposure times (2–12 h), unmodulated 900 MHz EMF induced DNA breaks and early activation of both p53‐dependent and ‐independent apoptotic pathways while longer continuous exposure (24–48 h) determined silencing of pro‐apoptotic signals and activation of genes involved in both intracellular (Bcl‐2) and extracellular (Ras and Akt1) pro‐survival signaling. Overall our results indicate that exposure to 900 MHz continuous wave, after inducing an early self‐defense response triggered by DNA damage, could confer to the survivor CCRF‐CEM cells a further advantage to survive and proliferate. J. Cell. Physiol. 198: 324–332, 2004. © 2003 Wiley‐Liss, Inc.     

Mobile phone electromagnetic radiation activates MAPK signaling and regulates viability in Drosophila

Mobile phones are widely used in the modern world. However, biological effects of electromagnetic radiation produced by mobile phones are largely unknown. In this report, we show biological effects of the mobile phone 835 MHz electromagnetic field (EMF) in the Drosophila model system. When flies were exposed to the specific absorption rate (SAR) 1.6 W/kg, which is the proposed exposure limit by the American National Standards Institute (ANSI), more than 90% of the flies were viable even after the 30 h exposure. However, in the SAR 4.0 W/kg strong EMF exposure, viability dropped from the 12 h exposure. These EMF exposures triggered stress response and increased the production of reactive oxygen species. The EMF exposures also activated extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling, but not p38 kinase signaling. Interestingly, SAR 1.6 W/kg activated mainly ERK signaling and expression of an anti-apoptotic gene, whereas SAR 4.0 W/kg strongly activated JNK signaling and expression of apoptotic genes. In addition, SAR 4.0 W/kg amplified the number of apoptotic cells in the fly brain. These findings demonstrate that the exposure limit on electromagnetic radiation proposed by ANSI triggered ERK-survival signaling but the strong electromagnetic radiation activated JNK-apoptotic signaling in Drosophila.     

Radiofrequency electromagnetic fields do not alter the cell cycle progression of C3H 10T and U87MG cells.

The effects of exposure to radiofrequency electromagnetic fields (RF EMFs) on cell cycle progression of mouse fibroblasts C3H 10T(1/2) and human glioma U87MG cells were determined by the flow cytometric bromodeoxyuridine pulse-chase method. Cells were exposed to a frequency-modulated continuous wave at 835.62 MHz or a code division multiple access RF EMF centered on 847.74 MHz at an average specific absorption rate of 0.6 W/kg. Five cell cycle parameters, including the transit of cells through G(1), G(2) and S phase and the probability of cell division, were examined immediately after the cells were placed in the fields or after they had been kept in the fields for up to 100 h. The only significant change observed in the study was that associated with C3H 10T(1/2) cell cultures moving into plateau phase toward the later times in the long-exposure experiment. No changes in the cell cycle parameters were observed in cells exposed to either mode of RF EMFs when compared to sham-exposed cells in either of the cell lines studied during the entire experimental period. The results show that exposure to RF EMFs, at the frequencies and power tested, does not have any effect on cell progression in vitro.     

Comparative study of cell cycle kinetics and induction of apoptosis or necrosis after exposure of human Mono Mac 6 cells to radiofrequency radiation

The possible harmful effects of radiofrequency electromagnetic fields (RF EMFs) are controversial. We have used human Mono Mac 6 cells to investigate the influence of RF EMFs in vitro on cell cycle alterations and BrdU uptake, as well as the induction of apoptosis and necrosis in human Mono Mac 6 cells, using flow cytometry after exposure to a 1,800 MHz, 2 W/kg specific absorption rate (SAR), GSM-DTX signal for 12 h. No statistically significant differences in the induction of apoptosis or necrosis, cell cycle kinetics, or BrdU uptake were detected after RF EMF exposure compared to sham or incubator controls. However, in the positive control cells treated with gliotoxin and PMA (phorbol 12 myristate-13 acetate), a significant increase in apoptotic and necrotic cells was seen. Cell cycle analysis or BrdU incorporation for 72 h showed no differences between RF EMF- or sham-exposed cells, whereas PMA treatment induced a significant accumulation of cells in G(0)/G(1)-phase and a reduction in S-phase cells. RF EMF radiation did not induce cell cycle alterations or changes in BrdU incorporation or induce apoptosis and necrosis in Mono Mac 6 cells under the exposure conditions used.     

Acute exposure to low-level CW and GSM-modulated 900 MHz radiofrequency does not affect Ba 2+ currents through voltage-gated calcium channels in rat cortical neurons

We have studied the non-thermal effects of radiofrequency (RF) electromagnetic fields (EMFs) on Ba(2+) currents (I Ba 2+) through voltage-gated calcium channels (VGCC), recorded in primary cultures of rat cortical neurons using the patch-clamp technique. To assess whether low-level acute RF field exposure could modify the amplitude and/or the voltage-dependence of I Ba 2+, Petri dishes containing cultured neurons were exposed for 1-3 periods of 90 s to 900 MHz RF-EMF continuous wave (CW) or amplitude-modulated according to global system mobile communication standard (GSM) during whole-cell recording. The specific absorption rates (SARs) were 2 W/kg for CW and 2 W/kg (time average value) for GSM-modulated signals, respectively. The results obtained indicate that single or multiple acute exposures to either CW or GSM-modulated 900 MHz RF-EMFs do not significantly alter the current amplitude or the current-voltage relationship of I Ba 2+, through VGCC.     

Effects of mobile phone electromagnetic fields on an auditory order threshold task

The effect of acute exposure to radio frequency electromagnetic fields (RF EMF) generated by mobile phones on an auditory threshold task was investigated. 168 participants performed the task while exposed to RF EMF in one testing session (either global system for mobile communication (GSM) or unmodulated signals) while in a separate session participants were exposed to sham signals. Lateralization effects were tested by exposing participants either on the left side or on the right side of the head. No significant effect of exposure to RF EMF was detected, suggesting that acute exposure to RF EMFs does not affect performance in the order threshold task.     

Effects of global system for mobile communications 1800 MHz radiofrequency electromagnetic fields on gene and protein expression in MCF-7 cells

Despite many studies over a decade, it still remains ambiguous as to the real biological effects induced by radiofrequency electromagnetic fields (RF EMF) utilized in mobile telephony. Here we investigated global gene and protein responses to RF EMF simulating the Global System for Mobile Communications (GSM) 1800 MHz signal in human breast cancer cell line MCF-7 using genomic and proteomic approaches. GeneChip analysis identified a handful of consistent changed genes after exposure to RF EMF at specific absorption rates (SAR) of up to 3.5 W/kg for 24 h. However, these differentially transcribed genes could not be further confirmed by real-time RT-PCR assay. Meanwhile, systematic proteome analysis of the MCF-7 cells revealed that a few but different proteins were differentially expressed under continuous or intermittent RF EMF exposure at SAR of 3.5 W/kg for 24 h or less, implying that the observed effects might have occurred by chance. Overall, the present study does not provide convincing evidence that RF EMF exposure under current experimental conditions can produce distinct effects on gene and protein expression in the MCF-7 cells.     

Microarray gene expression profiling of a human glioblastoma cell line exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field

The widespread use of mobile phones has led to public concerns about the health effects associated with exposure to radiofrequency (RF) fields. The paramount concern of most persons relates to the potential of these fields to cause cancer. Unlike ionizing radiation, RF fields used for mobile telecommunications (800-1900 MHz) do not possess sufficient energy to directly damage DNA. Most rodent bioassay and in vitro genotoxicity/mutation studies have reported that RF fields at non-thermal levels have no direct mutagenic, genotoxic or carcinogenic effects. However, some evidence has suggested that RF fields may cause detectable postexposure changes in gene expression. Therefore, the purpose of this study was to assess the ability of exposure to a 1.9 GHz pulse-modulated RF field for 4 h at specific absorption rates (SARs) of 0.1, 1.0 and 10.0 W/kg to affect global gene expression in U87MG glioblastoma cells. We found no evidence that non-thermal RF fields can affect gene expression in cultured U87MG cells relative to the nonirradiated control groups, whereas exposure to heat shock at 43 degrees C for 1 h up-regulated a number of typical stress-responsive genes in the positive control group. Future studies will assess the effect of RF fields on other cell lines and on gene expression in the mouse brain after in vivo exposure.     

An in vitro study of the effects of exposure to a GSM signal in two human cell lines: monocytic U937 and neuroblastoma SK-N-SH

The use of mobile phones is increasing, which also increases the population's exposure to global system of mobile communications (GSM) signals. Questions of safety and possible biological effects are of concern and to date, remain largely unanswered. In order to examine possible biological effects of a GSM-like signal at a cellular level, we exposed two human cell lines (one of neuronal (SK-N-SH) and the other of monocytoid (U937) origin) to a 900 MHz RF signal, pulsed at 217 Hz, producing a specific absorption rate (SAR) of 0.2 W/kg. Putative effects were assessed by comparing radiofrequency-exposed cells to sham-exposed cells using a variety of assay techniques. For the cell line SK-N-SH, effects were specifically assessed by gene microarray, followed by real-time PCR of the genes of interest, Western blot analysis was used to measure heat shock protein levels, and flow cytometry to measure cell cycle distributions and apoptosis. Effects of radiofrequency on the cell line U937 were assessed by cell viability and cell cycle analysis. From our study of these two cell lines, we found no significant difference between sham-exposed versus radiofrequency-exposed cells in any of the assays or conditions examined.     

Effect of 900 MHz radio frequency radiation on beta amyloid protein, protein carbonyl, and malondialdehyde in the brain

Recently, many studies have been carried out in relation to 900 MHz radiofrequency radiation (RF) emitted from a mobile phone on the brain. However, there is little data concerning possible mechanisms between long-term exposure of RF radiation and biomolecules in brain. Therefore, we aimed to investigate long-term effects of 900 MHz radiofrequency radiation on beta amyloid protein, protein carbonyl, and malondialdehyde in the rat brain. The study was carried out on 17 Wistar Albino adult male rats. The rat heads in a carousel were exposed to 900 MHz radiofrequency radiation emitted from a generator, simulating mobile phones. For the study group (n: 10), rats were exposed to the radiation 2 h per day (7 days a week) for 10 months. For the sham group (n: 7), rats were placed into the carousel and the same procedure was applied except that the generator was turned off. In this study, rats were euthanized after 10 months of exposure and their brains were removed. Beta amyloid protein, protein carbonyl, and malondialdehyde levels were found to be higher in the brain of rats exposed to 900 MHz radiofrequency radiation. However, only the increase of protein carbonyl in the brain of rats exposed to 900 MHz radiofrequency radiation was found to be statistically significant (p<0.001). In conclusion, 900 MHz radiation emitted from mobile/cellular phones can be an agent to alter some biomolecules such as protein. However, further studies are necessary.     

Effects of exposure of newborn patched1 heterozygous mice to GSM, 900 MHz

Patched1 heterozygous knockout mice (Ptc1+/-), an animal model of multiorgan tumorigenesis in which ionizing radiation dramatically accelerates tumor development, were used to study the potential tumorigenic effects of electromagnetic fields (EMFs) on neonatal mice. Two hundred Ptc1+/- mice and their wild-type siblings were enrolled in this study. Newborn mice were exposed to 900 MHz radiofrequency radiation (average SAR: 0.4 W/kg for 5 days, 0.5 h twice a day) or were sham exposed. We found that RF EMFs simulating the Global System for Mobile Communications (GSM) did not affect the survival of the mice, because no statistically significant differences in survival were found between exposed and sham-exposed animals. Also, no effects attributable to radiofrequency radiation were observed on the incidence and histology of Ptc1-associated cerebellar tumors. Moreover, the skin phenotype was analyzed to look for proliferative effects of RF EMFs on the epidermal basal layer and for acceleration of preneoplastic lesions typical of the basal cell carcinoma phenotype of this model. We found no evidence of proliferative or promotional effects in the skin from neonatal exposure to radiofrequency radiation. Furthermore, no difference in Ptc1-associated rhabdomyosarcomas was detected between sham-exposed and exposed mice. Thus, under the experimental conditions tested, there was no evidence of life shortening or tumorigenic effects of neonatal exposure to GSM RF radiation in a highly tumor-susceptible mouse model.     

Free radical release and HSP70 expression in two human immune-relevant cell lines after exposure to 1800 MHz radiofrequency radiation

The goal of this study was to investigate whether radiofrequency (RF) electromagnetic-field (EMF) exposure at 1800 MHz causes production of free radicals and/or expression of heat-shock proteins (HSP70) in human immune-relevant cell systems. Human Mono Mac 6 and K562 cells were used to examine free radical release after exposure to incubator control, sham, RF EMFs, PMA, LPS, heat (40 degrees C) or co-exposure conditions. Several signals were used: continuous-wave, several typical modulations of the Global System for Mobile Communications (GSM): GSM-non DTX (speaking only), GSM-DTX (hearing only), GSM-Talk (34% speaking and 66% hearing) at specific absorption rates (SARs) of 0.5, 1.0, 1.5 and 2.0 W/kg. Heat and PMA treatment induced a significant increase in superoxide radical anions and in ROS production in the Mono Mac 6 cells when compared to sham and/or incubator conditions. No significant differences in free radical production were detected after RF EMF exposure or in the respective controls, and no additional effects on superoxide radical anion production were detected after co-exposure to RF EMFs+PMA or RF EMFs+LPS. The GSM-DTX signal at 2 W/kg produced a significant difference in free radical production when the data were compared to sham because of the decreasing sham value. This difference disappeared when data were compared to the incubator controls. To determine the involvement of heat-shock proteins as a possible inhibitor of free radical production, we investigated the HSP70 expression level after different RF EMF exposures; no significant effects were detected.     

Low-level exposure to radiofrequency electromagnetic fields: Health effects and research needs

The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments. It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated. Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups. Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further. Bioelectromagnetics 19:1–19, 1998. © 1998 Wiley-Liss, Inc.     

Effect of 900 MHz Radio Frequency Radiation on Beta Amyloid Protein,Protein Carbonyl,and Malondialdehyde in the Brain

Recently, many studies have been carried out in relation to 900 MHz radiofrequency radiation (RF) emitted from a mobile phone on the brain. However, there is little data concerning possible mechanisms between long-term exposure of RF radiation and biomolecules in brain. Therefore, we aimed to investigate long-term effects of 900 MHz radiofrequency radiation on beta amyloid protein, protein carbonyl, and malondialdehyde in the rat brain. The study was carried out on 17 Wistar Albino adult male rats. The rat heads in a carousel were exposed to 900 MHz radiofrequency radiation emitted from a generator, simulating mobile phones. For the study group (n: 10), rats were exposed to the radiation 2 h per day (7 days a week) for 10 months. For the sham group (n: 7), rats were placed into the carousel and the same procedure was applied except that the generator was turned off. In this study, rats were euthanized after 10 months of exposure and their brains were removed. Beta amyloid protein, protein carbonyl, and malondialdehyde levels were found to be higher in the brain of rats exposed to 900 MHz radiofrequency radiation. However, only the increase of protein carbonyl in the brain of rats exposed to 900 MHz radiofrequency radiation was found to be statistically significant (p < 0.001).

In conclusion, 900 MHz radiation emitted from mobile/cellular phones can be an agent to alter some biomolecules such as protein. However, further studies are necessary.     

Chronic electromagnetic field exposure decreases HSP70 levels and lowers cytoprotection

Electromagnetic field (EMF) exposures have been shown to induce heat shock proteins (HSPs), which help to maintain the conformation of cellular proteins during periods of stress. We have previously reported that short-term exposure of chick embryos to either 60 Hz (extremely low frequency: ELF), or radio-frequency (RF: 915 MHz) EMFs induce protection against hypoxia. Experiments presented in the current report are based on a study in which long-term (4 days), continuous exposure to ELF-EMFs decreased protection against ultraviolet radiation. Based on this result, it was hypothesized that de-protection against hypoxia should also occur following long-term, continuous, or daily, repeated exposures to EMFs. To test this hypothesis, chick embryos were exposed to ELF-EMFs (8 microT) continuously for 4 days, or to ELF or RF (3.5 mW incident power)-EMFs repeated daily (20, 30, or 60 min once or twice daily for 4 days). Several of the exposure protocols yielded embryos that had statistically significant decreases in protection against hypoxic stress (continuous and 30 or 60 min ELF twice daily; or 30 or 60 min once daily RF). This is consistent with our finding that following 4 days of ELF-EMF exposure, HSP70 levels decline by 27% as compared to controls. In addition, the superposition of ELF-EMF noise, previously shown to minimize ELF-EMF induced hypoxia protection, inhibited hypoxia de-protection caused by long term, continuous ELF or daily, repeated RF exposures. This EMF-induced decrease in HSP70 levels and resulting decline in cytoprotection suggests a mechanism by which daily exposure (such as might be experienced by mobile phone users) could enhance the probability of cancer and other diseases.     

Cadmium results in accumulation of autophagosomes-dependent apoptosis through activating Akt-impaired autophagic flux in neuronal cells

Environmental exposure to cadmium (Cd) links to neurodegenerative disorders. Autophagy plays an important role in controlling cell survival/death. However, how autophagy contributes to Cd's neurotoxicity remains enigmatic. Here, we show that Cd induced significant increases in autophagosomes with a concomitant elevation of LC3-II and p62 in PC12 cells and primary neurons. Using autophagy inhibitor 3-MA, we demonstrated that Cd-increased autophagosomes contributed to neuronal apoptosis. Impairment of Cd on autophagic flux was evidenced by co-localization of mCherry and GFP tandem-tagged LC3 puncta in the cells. This is further supported by the findings that administration of chloroquine (CQ) potentiated the basic and Cd-elevated LC3-II and p62 levels, autophagosome accumulation and cell apoptosis, whereas rapamycin relieved the effects in the cells in response to Cd. Subsequently, we noticed that Cd evoked the phosphorylation of Akt and BECN1. Silencing BECN1 and especially expression of mutant BECN1 (Ser295A) attenuated Cd-increased autophagosomes and cell death. Of note, inhibition of Akt with Akt inhibitor X, or ectopic expression of dominant negative Akt (dn-Akt), in the presence or absence of 3-MA, significantly alleviated Cd-triggered phosphorylation of Akt and BECN1, autophagosomes, and apoptosis. Importantly, we found that Cd activation of Akt functioned in impairing autophagic flux. Collectively, these results indicate that Cd results in accumulation of autophagosomes-dependent apoptosis through activating Akt-impaired autophagic flux in neuronal cells. Our findings underscore that inhibition of Akt to improve autophagic flux is a promising strategy against Cd-induced neurotoxicity and neurodegeneration.