Pulsed magnetic field increases the effect of ultraviolet C radiation and thermal shock in aged yeasts / El campo magnético pulsado aumenta el efecto de la radiación ultravioleta C y el choque térmico en levaduras envejecidas

The study of the effects of the magnetic field (MF) on living matter continues to be a dilemma. Until now, the interaction mechanisms of MF with living matter that explain the observed phenomena are unknown. Despite the existing literature and the multiple effects described to date, there are few published articles that study the combined effect of MF with other physical agents during the cellular aging process. In this sense, the aim of this work is to study whether low frequency and intensity pulsed and sinusoidal MF exposure produce alterations in the cell killing effect of ultraviolet C (UVC) radiation and thermal shock during the chronological aging of S. cerevisiae. Yeast cells were exposed to 2.45 mT (50 Hz) sinusoidal MF and 1.5 mT (25 Hz) pulsed MF, during 40 days of aging, in combination with UVC radiation (50 J/m2) and/or thermal shock (52°C). Cell survival was evaluated by clonogenic assay. The exposure of yeast to pulsed MF produces an acceleration of aging, which is not observed in cells exposed to sinusoidal MF. The pulsed MF modifies the cellular response to damaging agents only in aged S. cerevisiae cells. In this sense, the pulsed MF applied increases the damage induced by UVC radiation and by thermal shock. In contrast, the sinusoidal MF used has no effect.(AU)

Molecular Mechanisms of Resistance to Ionizing Radiation in S. cerevisiae and Its Relationship with Aging, Oxidative Stress, and Antioxidant Activity.

The repair of the damage produced to the genome and proteome by the action of ionizing radiation, oxidizing agents, and during aging is important to maintain cellular homeostasis. Many of the metabolic pathways influence multiple processes. In this way, this work aims to study the relationship between resistance/response to ionizing radiation, cellular aging, and the response mechanisms to oxidative stress, free radicals, reactive oxygen species (ROS), and antioxidant activity in the yeast S. cerevisiae. Systems biology allows us to use tools that reveal the molecular mechanisms common to different cellular response phenomena. The results found indicate that homologous recombination, non-homologous end joining, and base excision repair pathways are the most important common processes necessary to maintain cellular homeostasis. The metabolic routes of longevity regulation are those that jointly contribute to the three phenomena studied. This study proposes eleven common biomarkers for response/resistance to ionizing radiation and aging (EXO1, MEC1, MRE11, RAD27, RAD50, RAD51, RAD52, RAD55, RAD9, SGS1, YKU70) and two biomarkers for response/resistance to radiation and oxidative stress, free radicals, ROS, and antioxidant activity (NTG1, OGG1). In addition, it is important to highlight that the HSP104 protein could be a good biomarker common to the three phenomena studied.

Pulsed magnetic field increases the effect of ultraviolet C radiation and thermal shock in aged yeasts.

The study of the effects of the magnetic field (MF) on living matter continues to be a dilemma. Until now, the interaction mechanisms of MF with living matter that explain the observed phenomena are unknown. Despite the existing literature and the multiple effects described to date, there are few published articles that study the combined effect of MF with other physical agents during the cellular aging process. In this sense, the aim of this work is to study whether low frequency and intensity pulsed and sinusoidal MF exposure produce alterations in the cell killing effect of ultraviolet C (UVC) radiation and thermal shock during the chronological aging of S. cerevisiae. Yeast cells were exposed to 2.45 mT (50 Hz) sinusoidal MF and 1.5 mT (25 Hz) pulsed MF, during 40 days of aging, in combination with UVC radiation (50 J/m2) and/or thermal shock (52°C). Cell survival was evaluated by clonogenic assay. The exposure of yeast to pulsed MF produces an acceleration of aging, which is not observed in cells exposed to sinusoidal MF. The pulsed MF modifies the cellular response to damaging agents only in aged S. cerevisiae cells. In this sense, the pulsed MF applied increases the damage induced by UVC radiation and by thermal shock. In contrast, the sinusoidal MF used has no effect.

Genomic DNA damage induced by co-exposure to DNA damaging agents and pulsed magnetic field.

PURPOSE: Many articles describe the effects of extremely low-frequency magnetic fields (MFs) on DNA damage induction. However, the mechanism of MF interaction with living matter is not yet known with certainty. Some works suggest that MF could induce an increase in the efficacy of reactive oxygen species (ROS) production. This work investigates whether pulsed MF exposure produces alterations in genomic DNA damage induced by co-exposure to DNA damaging agents (bleomycin and methyl methanesulfonate (MMS)). MATERIALS AND METHODS: Genomic DNA, prepared from S. cerevisiae cultures, was exposed to pulsed MF (1.5 mT peak, 25 Hz) and MMS (0-1%) (15-60 min), and to MF and bleomycin (0-0.6 IU/mL) (24-72 h). The damage induced to DNA was evaluated by electrophoresis and image analysis. RESULTS: Pulsed MF induced an increment in the level of DNA damage produced by MMS and bleomycin in all groups at the exposure conditions assayed. CONCLUSIONS: Pulsed MF could modulate the cytotoxic action of MMS and bleomycin. The observed effect could be the result of a multifactorial process influenced by the type of agent that damages DNA, the dose, and the duration of the exposure to the pulsed MF.

Relationship between heat shock proteins and cellular resistance to drugs and ageing.

BACKGROUND AND AIMS: Ageing is a multifactorial degenerative process which causes a decrease in the cellular capacity for repair and adaptation to external stressors. In this way, it is important to maintain the proper balance of the proteome. Heat shock proteins (HSP) will intervene in this balance, which are responsible for the correct assembly, folding and translocation of other proteins when cells are subjected to stressors. This type of protein is overexpressed in human tumor cells, while its deficit, both in function and quantity, contributes to ageing processes. The present work aims to analyze the response of cells from studies carried out in normal and tumor cells that are subjected to stressors. METHODS AND RESULTS: A PubMed search was performed using the keywords "cell ageing, cell longevity, resistance, HSP, heat shock proteins, thermal shock proteins". This search generated 212 articles. Subsequently, a series of inclusion and exclusion criteria were applied to select the articles of interest to be evaluated. Normal cells subjected to external stressors at low doses increase the number of HSP, causing them to become more resistant. In addition, tumor cells expressing high levels of HSP show greater resistance to treatment and increased cell replication. HSP intervene in the cellular resistance of both normal and tumor cells. CONCLUSIONS: In the case of normal cells, the increase in HSP levels makes them respond effectively to an external stressor, increasing their resistance and not causing cell death. In the case of tumor cells, there is an increase in resistance to treatment.

Factors and molecular mechanisms of radiation resistance in cancer cells.

PURPOSE: The aim of this work is to review the published studies on radiation resistance mechanisms and molecular markers involved in different tumors. The revision has been focused in the last 5 years (2016-2021). CONCLUSIONS: Radioresistance is a cause of concern as it causes failure of radiation therapy and subsequent tumor relapse. Combination chemotherapy and radiation therapy are clinically successful in treating many types of tumors. Despite continued improvements in cancer treatment, locoregional recurrence or metastatic spread continues to occur in a high proportion of patients after being treated with radiation therapy or combination treatments. There is strong evidence that cancer stem cells contribute to radiation resistance, contributing to treatment failure. The mechanisms of radiation resistance in different tumors are not fully understood. A better understanding of cancer stem cells and the associated signaling pathways that regulate radiation resistance will open up new strategies for treating cancer by radiation therapy. Radiation can damage malignant cells mainly by the induction of DNA double-strand breaks. However, in some tumors appear resistant cells that repopulate the tumor following therapy leading over time to the failure of the treatment. Native mechanisms and induced pathways are the cause of radiation resistance. It has been described that numerous molecular markers acting through numerous mechanisms of action involved in radiation resistance, such as apoptosis resistance, alterations of cell growth, proliferation and DNA repair, hypoxia, increase in invasiveness and migration capacity, cell cycle alterations, and expression of heat shock proteins, among others. Therefore, resistance to radiation is a multifactorial phenomenon that, in different cell types, occurs through different regulatory mechanisms in which different molecules intervene. Resistance can be acquired by altering different regulatory pathways in different tumors. The knowledge of radiation resistance markers could help in the classification and treatment of patients with more aggressive tumors.

Evidences of the (400 MHz - 3 GHz) radiofrequency electromagnetic field influence on brain tumor induction.

Due to the massive increase in non-ionizing radiation emitting devices, the social concern about the possible malignancy to its exposure has increased the research interest. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) included the radiofrequency electromagnetic field (RF-EMF) of mobile phones on the category 2B as 'possibly' carcinogenic to humans. Epidemiological studies noticed a causal association between the exposure to RF-EMF and the incidence of brain neoplasm in different populations, since this is the organ with the highest specific absorption rate. The fact that so many of the ipsilateral tumors found are statistically significant with RF-EMF exposure provides weight suggesting causality. In this way, the higher the exposure (ipsilateral vs contralateral), the longer the cumulative exposure (hours of exposure) and the longer the latency (beyond 10 years); the greater the risk. In addition, considering together all of these parameters suggest a strong causality.

Exposure of S. cerevisiae to pulsed magnetic field during chronological aging could induce genomic DNA damage.

This study evaluates the DNA damage induced by pulsed magnetic field (MF) on S. cerevisiae cells exposed during chronological aging. Samples were exposed to 25 Hz pulsed MF (1.5mT, 8 h/day) while cells were aging chronologically. Clonogenic drop test was used to study cellular survival and the mutation frequency was evaluated by scoring the spontaneous revertant mutants. DNA damage analysis was performed after aging by electrophoresis and image analysis. Yeast cells aged during 40 days of exposure showing that pulsed MF exposure induced a premature aging. In addition, a gradual increase in spontaneous mutants was found in pulsed MF samples in relation to unexposed controls. An increase in DNA degradation, over the background level in relation to controls, was observed at the end of the exposure period. In conclusion, exposure of S. cerevisiae cells to pulsed MF during chronological aging could induce genomic DNA damage.

Growth alteration of Allium cepa L. roots exposed to 1.5 mT, 25 Hz pulsed magnetic field.

The response of plants to magnetic fields (MF) is not fully understood. This work studies the effects of pulsed MF on the germination and growth of Allium cepa roots. Onions were exposed to 25Hz, 1.5mT, 33h. Pulsed MF was generated by a Helmholtz-type equipment that generated rectangular voltage pulses. The results showed that fewer roots grew in the specimens exposed to pulsed MF (14±6 roots on day 1 to 21±8 on day 4) than in the control groups (32±17 to 48±23) (p<0.05 Friedman). Control specimens showed a root mean length of 7±4 mm (day 1) and 24±10 mm (day 4). The specimens treated with pulsed MF showed a length of 4±2 mm (day 1), reaching 18±9 mm on day 4 (p<0.001 ANOVA). In conclusion, the exposure of Allium cepa specimens to 25Hz, 1.5mT pulsed MF during 33h produces a decrease in the germination and growth of roots.

Identification of new proteins related with cisplatin resistance in Saccharomyces cerevisiae.

The aim of this study is to select a cisplatin-resistant Saccharomyces cerevisiae strain to look for new molecular markers of resistance and the identification of mechanisms/interactions involved. A resistant strain was obtained after 80 days of cisplatin exposure. Then, total protein extraction, purification, and identification were carried out, in wild-type (wt) and resistant strains, by tandem mass spectrometry using a "nano HPLC-ESI-MS/MS" ion trap system. The increase in the exponentially modified protein abundance index (emPAI) (resistant vs wt strains) was calculated to study the increase in protein expression. "Genemania" software ( http://www.Genemania.org/ ) was used to compare the effects, functions, and protein interactions. KEGG tool was used for metabolic pathway analysis. Data are available via ProteomeXchange with identifier PXD020665. The cisplatin-resistant strain showed 2.5 times more resistance than the wt strain for the inhibitory dose 50% (ID50) value (224 µg/ml vs 89.68 µg/ml) and 2.78 times more resistant for the inhibitory dose 90% (ID90) value (735.2 µg/ml vs 264.04 µg/ml). Multiple deregulated proteins were found in the glutathione and carbon metabolism, oxidative phosphorylation, proteasome, glycolysis and gluconeogenesis, glyoxylate metabolism, fatty acid degradation pathway, citric acid cycle, and ribosome. The most overexpressed proteins in the cisplatin-resistant strain were related to growth and metabolism (QCR2, QCR1, ALDH4, ATPB, ATPA, ATPG, and PCKA), cell structure (SCW10), and thermal shock (HSP26). The results suggest that these proteins could be involved in cisplatin resistance. The resistance acquisition process is complex and involves the activation of multiple mechanisms that interact together. KEY POINTS: • Identification of new proteins/genes related to cisplatin resistance • Increased expression of QCR2/QCR1/ALDH4/ATPB/ATPA/SCW10/HSP26/ATPG and PCKA proteins • Multiple molecular mechanisms that interact together are involved in resistance.

Effect of low frequency magnetic field on efficiency of chromosome break repair.

DNA repair is essential to maintain genome integrity. There is scientific evidence that exposure to magnetic fields (MF) can produce alterations in DNA repair without clear conclusions. This work aims to study the cellular response to and repair of a very deleterious type of DNA damage, the DNA double strand break (DSB), in S. cerevisiae, under MF exposure. In S. cerevisiae cells, pairs of DSB were induced enzymatically by HO endonuclease by plating the cells on Galactose-containing media. The repair processes took place under exposure to a 50Hz, 2.45mT sinusoidal MF during 21 days. MF was generated by a pair of Helmholtz coils. MF induced 1.29- and 1.5-fold increase in the number of colonies grown at day 21 of exposure in relation to untreated controls for Pho91 and Rmd5 strain, respectively. In relation to the kinetics of DSB repair during MF exposure, a higher increase (55.56-fold) in DNA reparation was observed at day 15 for Rmd5 strain in relation to the slight increment (1.18-fold) found for Pho91 strain. The results suggest that long-term MF exposure could increase the DNA repair activity and there may be a relationship between the position of the DSB and the distance to the centromere.

Effect of sinusoidal and pulsed magnetic field exposure on the chronological aging and cellular stability of S. cerevisiae.

Purpose: The aim of this study is to investigate the effects of low frequency and intensity sinusoidal magnetic field (SMF) and pulsed magnetic field (PMF) exposure on the chronological aging and cellular stability of Saccharomyces cerevisiae.Materials and methods: The S. cerevisiae wild type strain (WS8105-1C) was exposed to SMF (2.45 mT, 50 Hz, continuous) and PMF (1.5 mT, 25 Hz, 8 h/day). Chronological aging was evaluated during 40 days. Survival was assayed by clonogenic assay and drop test. Cellular stability was studied by spontaneous mutation count and the index of respiratory competence (IRC).Results: We found that exposure to PMF produces an acceleration of cellular chronological aging, not observed in the groups treated with SMF. A decrease in the spontaneous frequency of mitochondrial mutation during aging was observed in PMF-treated samples. However, no alterations in the IRC during aging were found for both, SMF and PMF, treatments.Conclusions: Exposure to PMF produces the acceleration of aging and an alteration in cellular stability.