Conferring drug resistance by MDR1 gene transfection increases susceptibility to irradiation and lipid peroxidation in 3T3 cell line

Mazzanti, Roberto; Fantappiè, Ornella; Fabrizio, Paola; Pacini, Stefania; Relli, P; Casamassima, F.; Milano, F.; Ruggiero, Marco

doi:10.1016/0891-5849(95)02063-2

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…[16] In particular, resistance to oxidative stress is associated with a high content of vitamin E. [16] A significant role of P-gp per se in promoting resistance of the cell membranes to lipid peroxidation seems to be excluded given that transfection of NIH-3T3 cells with the MDR-1 gene has been shown to increase sensitivity to radiation and iron-stimulated lipid peroxidation. [18] These data suggest that some other mechanisms besides P-gp over-expression could be involved in explaining the differences in resistance to lipid peroxidation between the MDR phenotype expressing cell clones and their parental drug-sensitive cells.…”

Section: Discussionmentioning

confidence: 96%

“…On the contrary, we demonstrated that transfection of the MDR-1 gene in NIH-3T3 cells increases susceptibility to both iron-stimulated lipid peroxidation and radiation. [18] The increased resistance to oxidative stress observed in HCC cells expressing MDR phenotype is most likely due to an increase in antioxidant defenses such as the cell content of vitamin E rather than to the over-expression of P-gp. [16] Among antioxidants, only vitamin E cell content was significantly higher in P1(0.5) in comparison with P5.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin E Protects DNA from Oxidative Damage in Human Hepatocellular Carcinoma Cell Lines

Fantappiè

Lodovici

Fabrizio

et al. 2004

Free Radical Research

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Expression of multiple drug resistant (MDR) phenotype and over-expression of P-glycoprotein (P-gp) in the human hepatocellular carcinoma (HCC) cell clone P1(0.5), derived from the PLC/PRF/5 cell line (P5), are associated with strong resistance to oxidative stress and a significant (p < 0.01) increase in intracellular vitamin E content as compared with the parental cell line. This study evaluates the role of vitamin E in conferring resistance to drugs and oxidative stress in P1(0.5) cells. Parental drug-sensitive cells, P5, were incubated in alpha-tocopherol succinate (alpha-TS, 5 microM for 24 h) enriched medium to increase intracellular vitamin E content to levels comparable to those observed in P1(0.5) cells at basal conditions. Susceptibility to lipid peroxidation and oxidative DNA damage were assessed by measuring the concentration of thiobarbituric-reactive substances (TBARS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) at basal and after experimental conditions. Cell capacity to form colonies and resistance to doxorubicin were also studied. P5 cells, treated with alpha-TS, became resistant to ADP-Fe3+ and to ionizing radiation-induced lipid peroxidation as P1(0.5) cells. Exposure to ADP-Fe3+ or ionizing radiation increased TBARS and the 8-OHdG content in the P5 cells, while vitamin E enrichment abolished these effects. Irradiation doses at 5 cGy increased TBARS and 8-OHdG. They also inhibited cell capacity to form colonies in the untreated P5 cells. Incubation with alpha-TS fully reverted this effect and significantly (p < 0.01) reduced the inhibitory effect of cell proliferation induced by irradiation doses at >500 cGy. Resistance to doxorubicin was not affected by alpha-TS. These observations demonstrate the role of vitamin E in conferring protection from lipid peroxidation, ionizing radiation and oxidative DNA damage on the human HCC cell line. They also rule out any role of P-gp over-expression as being responsible for these observations in cells with MDR phenotype expression.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Vitamin E Protects DNA from Oxidative Damage in Human Hepatocellular Carcinoma Cell Lines

Fantappiè

Lodovici

Fabrizio

et al. 2004

Free Radical Research

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“…For more than thirty years, I have studied the biological effects of different types of energy, ranging from static magnetic fields to ionizing and non-ionizing radiations and ultrasounds, on normal and transformed cells in culture, embryos and organisms, with particular reference to changes in signal transduction, gene expression, cell morphology and clinical responses (Casamassima et al, 1989;Orlandini et al, 1991;Ruggiero et al, 1992;Vincenzini et al, 1993;Pacini et al, 1994a;1994b;Chiarugi et al, 1995;Mazzanti et al, 1996;Santucci et al, 1996;Pacini et al, 1999a;1999b;1999c;Casamassima et al, 1999;Pacini et al, 2002;2003;Ruggiero et al, 2004;Pacini et al, 2006;Ruggiero, 2008;Ruggiero et al, 2013;Bradstreet et al, 2014;Ruggiero and Aterini, 2015;Klinghardt, 2017;Branca et al, 2018). Certain types of eukaryotic cells, notably certain types of cancer cells (Vincenzini et al, 1993;Pacini et al, 1994a;1994b;Chiarugi et al, 1995;Mazzanti et al, 1996;Santucci et al, 1996;Pacini et al, 1999a), show resistance to the killing effects of ionizing radiations, a phenomenon that, in the context of radiotherapy of cancer, may represent an obstacle to effective treatment (Casamassima et al, 1999). Most prokaryotic cells are sensitive to the killing effects of ionizing radiations and even to weak electromagnetic fields such as those generated by the physiologic electric activity of human cells in vivo (Ruggiero and Aterini, 2015).…”

Section: Introductionmentioning

confidence: 99%

Experimental Evidence for the Role of Natural Radioactivity in Influencing Viability of Commensal Microorganisms

Ruggiero¹

2021

American Journal of Immunology

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To investigate the feasibility of culturing edible microbes, classified as probiotics for human consumption, in commercially available, naturally radioactive, mineral water; to compare their viability with that of the same microbes cultured in deuterium-depleted water. A diversified array of probiotics was cultured in two different naturally radioactive mineral waters, or in deuterium-depleted water in order to assess the effects of different culture conditions on microbial viability. Prebiotic microbes for human consumption (cyanobacteria) that are extremely resistant to radiations, were cultured together with the probiotics in a naturally radioactive carbonated mineral water containing silica from vegetal origin introduced to enhance horizontal gene transfer. This co-culture had the goal of transferring radiation resistance from the cyanobacteria to the probiotics. The experiments and the observations described in this study were conducted from April 2020 until March 2021. Culturing microbes in naturally radioactive mineral water yielded one order of magnitude more live microbial cells in comparison with culturing in deuterium-depleted water. In silico observations suggest that expression of DNA repair genes in cyanobacteria is induced by co-culturing conditions in a medium of carbonated mineral water naturally containing the radioactive isotopes 228 U and 226 Ra. The results presented in this study lay the foundation for the development of a novel approach to protection against electromagnetic fields comprising ionizing and non-ionizing radiations. In silico observations and preliminary results on subjects exposed to common electromagnetic fields under real-life conditions, support the hypothesis that co-cultures of radiation-resistant cyanobacteria and probiotics in naturally radioactive, carbonated mineral water may confer protection against the harmful effects of electromagnetic fields.

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“…The Pgp expression level is found to be correlated with the level of drug resistance in cancer. Transfection with mdr1 gene into the drug-sensitive cells can induce MDR phenomenon in cells (5). Inhibitor of Pgp, such as verapamil, the calcium channel blocker, which can block Pgp from effluxing drugs, was found to increase the drug sensitivity of cancer cells (6).…”

Section: Introductionmentioning

confidence: 99%

Facilitation of drug resistance development by γ-irradiation in human cancer cells

Kwok¹

2009

Oncol Rep

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Abstract. Hepatocellular carcinoma HepG2 cells (G cells)were subjected to selection first with Á-radiation and then doxorubicin (Dox). The radiation treatment consisted of 2 Gy for 10 days (G2) or 10 Gy for 2 days (G10) and the Dox treatment was continuous exposure for up to 10 μM. Compared with respective parental G, G2, G10 cells, the Doxselected cells showed mdr1 amplification/P-glycoprotein overexpression, Dox resistance and also less intracellular Dox accumulation. Verapamil reversed the drug resistance and increased the Dox accumulation in all cells. Decay in drug resistance and reduction in mdr1 amplification/P-glycoprotein overexpression were observed in the Dox-selected cells culturing in Dox-free condition. Among the Dox-selected cells, G2R cells showed the highest levels of drug resistance, mdr1 amplification, but the least resistance decay. Results from the study indicate the possible influence of radiation treatment on the development of drug resistance in cancer cells and it may even lead to a highly resistant phenotype.

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Conferring drug resistance by MDR1 gene transfection increases susceptibility to irradiation and lipid peroxidation in 3T3 cell line

Cited by 7 publications

References 21 publications

Vitamin E Protects DNA from Oxidative Damage in Human Hepatocellular Carcinoma Cell Lines

Vitamin E Protects DNA from Oxidative Damage in Human Hepatocellular Carcinoma Cell Lines

Experimental Evidence for the Role of Natural Radioactivity in Influencing Viability of Commensal Microorganisms

Facilitation of drug resistance development by γ-irradiation in human cancer cells

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