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Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response

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Abstract

Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response.

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Abbreviations

ADR:

Adriamicyne resistant cells

AO:

Amine oxidase

APAO:

Acetyl-polyamine oxidase

BER:

Base-excision-repair

BSAO:

Bovine serum amine oxidase

DSB:

Double strand break

DX:

Doxorubicin resistant

FAD:

Flavin-adenin-dinucleotide

H2O2 :

Hydrogen peroxide

IU:

International units

LNT:

Linear no-threshold

METC:

Mitochondrial electron transport chain

MDL 72527:

N1,N4-bis(2,3-butadienyl)-1,4-butanediaminedihydrochloride

MDR:

Multidrug resistant

NER:

Nucleotide-excision-repair

PA:

Polyamine

P-gp:

P-glycoprotein

ROS:

Reactive oxygen species

SMOX:

Spermine oxidase

SPD:

Spermidine

SPM:

Spermine

SSB:

Single strand break

TC-NER:

Transcription coupled-NER

TEM:

Transmission electron microscopy

JC-1:

5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolcarbocyanine iodide

WT:

Wild-type

References

  • Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, Protić M, Hübscher U, Egly JM, Wood RD (1995) Mammalian DNA nucleotide excision repair reconstituted with purified components. Cell 80:859–868

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Przybytkowski E, Mondovi B, Averill-Bates DA (1994) Heat enhancement of cytotoxicity induced by oxidation products of spermine in Chinese hamster ovary cells. Biochem Pharmacol 48:1181–1186

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Arancia G, Calcabrini A, Matarrese P, Mondovì B, Pietrangeli P (1995) Hyperthermia-induced biochemical and ultrastructural modifications in cultured cells. Exp Oncol 17:269–276

    Google Scholar 

  • Agostinelli E, Arancia G, Dalla Vedova L, Belli F, Marra M, Salvi M, Toninello A (2004) The biological functions of polyamine oxidation products by amine oxidases. Perspectives of clinical applications. Amino Acids 27:347–358

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Belli F, Dalla Vedova L, Marra M, Crateri P, Arancia G (2006a) Hyperthermia enhances cytotoxicity of amine oxidase and spermine on drug-resistant LoVo colon adenocarcinoma cells. Int J Oncol 28:1543–1553

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Belli F, Molinari A, Condello M, Palmigiani P, Dalla Vedova L, Marra M, Seiler N, Arancia G (2006b) Toxicity of enzymatic oxidation products of spermine to human melanoma cells (M14): sensitisation by heat and MDL 72527. Biochim Biophys Acta 1763:1040–1050

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Dalla Vedova L, Belli F, Condello M, Arancia G, Seiler N (2006c) Sensitization of human colon adenocarcinoma cells (LoVo) to reactive oxygen species by a lysosomotropic compound. Int J Oncol 29:947–955

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Tempera G, Molinari A, Salvi M, Battaglia V, Toninello A, Arancia G (2007) The physiological role of biogenic amines redox reactions in mitochondria. New perspectives in cancer therapy. Amino Acids 33:175–187

    CAS  PubMed  Google Scholar 

  • Agostinelli E, Condello M, Molinari A, Tempera G, Viceconte N, Arancia G (2009) Cytotoxicity of spermine oxidation products to multidrug resistant melanoma M14 ADR2 cells: sensitization by the MDL 72527 lysosomotropic compound. Intern J Oncol 35:485–498

    CAS  Google Scholar 

  • Amendola R, Bellini A, Cervelli M, Degan P, Marcocci L, Martini F, Mariottini P (2013) Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells. Biochim Biophysic Acta Rev Cancer 1755:15–24

    Google Scholar 

  • Arancia G, Calcabrini A, Marra M, Crateri P, Artico M, Martone A, Martelli F, Agostinelli E (2004) Mitochondrial alterations induced by serum amine oxidase and spermine on human multidrug resistant tumor cells. Amino Acids 26:273–282

    CAS  PubMed  Google Scholar 

  • Averill-Bates DA, Cherif A, Agostinelli E, Tanel A, Fortier G (2005) Antitumoral effect of native and immobilized bovine serum amine oxidase in a mouse melanoma model. Biochem Pharmacol 69:1693–1700

    CAS  PubMed  Google Scholar 

  • Babbar N, Casero RA Jr (2006) Tumor necrosis factor-A increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis. Cancer Res 66:11125–11130

    CAS  PubMed  Google Scholar 

  • Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    CAS  PubMed  Google Scholar 

  • Bates DA, Mackillop WJ (1990) The effect of hyperthermia in combination with melphalan on drug-sensitive and drug-resistant CHO cells in vitro. Br J Cancer 62:183–188

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bennett CB, Lewis AL, Baldwin KK, Resnick MA (1993) Lethality induced by a single site-specific double-strand breaks in a dispensible yeast plasmid. Proc Natl Acad Sci USA 90:5613–5617

    CAS  PubMed  Google Scholar 

  • Bianchi M, Bellini A, Cervelli M, Degan P, Marcocci L, Martini F, Scatteia M, Mariottini P, Amendola R (2007) Chronic sub-lethal oxidative stress by spermine oxidase over activity induces continuous DNA repair and hypersensitivity to radiation exposure. Biochim Biophys Acta Mol Cell Res 1773:774–783

    CAS  Google Scholar 

  • Bohr VA (2002) Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells. Free Radic Biol Med 32:804–812

    CAS  PubMed  Google Scholar 

  • Boonstra J, Post JA (2004) Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene 337:1–13

    CAS  PubMed  Google Scholar 

  • Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, Lubin JH, Preston DL, Preston RJ, Puskin JS, Ron E, Sachs RK, Samet JM, Setlow RB, Zaider M (2003) Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci USA 100:13761–13766

    CAS  PubMed  Google Scholar 

  • Brunk UT, Dalen H, Roberg K, Hellquist HB (1997) Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts. Free Radic Biol Med 23:616–626

    CAS  PubMed  Google Scholar 

  • Calcabrini A, Arancia G, Marra M, Crateri P, Befani O, Martone A, Agostinelli E (2002) Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug-resistant colon carcinoma cells (LoVo) than on their wild-type counterparts. Int J Cancer 99:43–52

    CAS  PubMed  Google Scholar 

  • Casero RA Jr, Marton LJ (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov 6:373–390

    CAS  PubMed  Google Scholar 

  • Cervelli M, Polticelli F, Federico R, Mariottini P (2003) Heterologous expression and characterization of mouse spermine oxidase. J Biol Chem 278:5271–5276

    CAS  PubMed  Google Scholar 

  • Cervelli M, Bellavia G, Fratini E, Amendola R, Polticelli F, Barba M, Federico R, Signore F, Gucciardo G, Grillo R, Woster PM, Casero RA Jr, Mariottini P (2010) Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm. BMC Cancer 10:555

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cervelli M, Amendola R, Polticelli F, Mariottini P (2012) Spermine oxidase: ten years after. Amino Acids 42:441–450

    CAS  PubMed  Google Scholar 

  • Cervelli M, Salvi D, Polticelli F, Amendola R and Mariottini P (2013) Structure–function relationships in the evolutionary framework of spermine oxidase. J Mol Evol (in press). doi:10.1007/s00239-013-9570-3

  • Coates PJ, Lorimore SA, Wright EG (2004) Damaging and protective cell signalling in the untargeted effects of ionizing radiation. Mutat Res 568:5–20

    CAS  PubMed  Google Scholar 

  • Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. Faseb J 17:1195–1214

    CAS  PubMed  Google Scholar 

  • Dahl O (1994) Mechanisms of thermal enhancement of chemotherapeutic cytotoxicity. In: Urano M, Douple E (eds) Hyperthermia and Oncology. Utrecht: VSP 4:9–28

  • Dai H, Kramer DL, Yanag C, Murti KG, Porter CW, Cleveland JL (1999) The polyamine oxidase inhibitor MDL 72527 selectively induces apoptosis of transformed haematopoietic cells through lysosomotropic effects. Cancer Res 59:4944–4955

    CAS  PubMed  Google Scholar 

  • Day TK, Zeng G, Hooker AM, Bhat M, Scott BR, Turner DR, Sykes PJ (2006) Extremely low priming doses of X radiation induce an adaptive response for chromosomal inversions in pKZ1 mouse prostate. Radiat Res 166:757–766

    CAS  PubMed  Google Scholar 

  • De Laat WL, Jaspers NGJ, Hoeijmakers JHJ (1999) Molecular mechanism of nucleotide excision repair. Genes Dev 13:768–785

    PubMed  Google Scholar 

  • De Toledo SM, Asaad N, Venkatachalam P, Li L, Howell RW, Spitz DR, Azzam EI (2006) Adaptive responses to low-dose/low-dose-rate g-rays in normal human fibroblasts: the role of growth architecture and oxidative metabolism. Radiat Res 166:849–857

    PubMed  Google Scholar 

  • Demers N, Agostinelli E, Averill-Bates DA, Fortier G (2001) Immobilization of native and poly(ethylene glycol)-treated (‘PEGylated’) bovine serum amine oxidase into a biocompatible hydrogel. Biotech Appl Biochem 33:201–207

    CAS  Google Scholar 

  • Dennog C, Hartmann A, Frey G, Speit G (1996) Detection of DNA damage after hyperbaric oxygen (HBO) therapy. Mutagenesis 11:605–609

    CAS  PubMed  Google Scholar 

  • Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, Cascante M (2013) Targeting cell cycle regulation in cancer therapy. Pharmacol Ther 138:255–271

    CAS  PubMed  Google Scholar 

  • Dizdaroglu M (2005) Base-excision repair of oxidative DNA damage by DNA glycosylases. Mutat Res 591:45–59

    CAS  PubMed  Google Scholar 

  • Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J (2000) Colorectal cancer prevention in ulcerative colitis: a case–control study. Aliment Pharmacol Ther 14:145–153

    CAS  PubMed  Google Scholar 

  • Eccles LJ, Lomax ME, O’Neill P (2009) Hierarchy of lesion processing governs the repair, double-strand break formation and mutability of three-lesion clustered DNA damage. Nucleic Acids Res 38:1123–1134

    PubMed Central  PubMed  Google Scholar 

  • Fardin P, Barla A, Mosci S, Rosasco L, Verri A, Versteeg R, Caron HN, Molenaar JJ, Ora I, Eva A, Puppo M, Varesio L (2010) A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients. Molecular Cancer 9:185–200

    PubMed Central  PubMed  Google Scholar 

  • Feuerstein BG, Pattabiraman N, Marton LJ (1986) Spermine-DNA interactions: a theoretical study. Proc Natl Acad Sci USA 16:5948–5952

    Google Scholar 

  • Fratini E, Licursi V, Artibani M, Kobos K, Colautti P, Negri R, Amendola R (2011) Dose-dependent onset of regenerative program in neutron irradiated mouse skin. PlosOne 6:e19242

    CAS  Google Scholar 

  • Goldman M (1996) Cancer risk of low-level exposure. Science 271:1821–1822

    CAS  PubMed  Google Scholar 

  • Goodhead DT (1994) Initial events in the cellular effects of ionizing radiations: clustered damage to DNA. Int J Radiat Biol 65:7–17

    CAS  PubMed  Google Scholar 

  • Goodwin AC, Jadallah S, Toubaji A, Lecksell K, Hicks JL, Kowalski J, Bova GS, De Marzo AM, Netto GJ, Casero RA Jr (2008) Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues. Prostate 68:766–772

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gottesman MM, Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62:385–427

    CAS  PubMed  Google Scholar 

  • Guicciardi ME, Leist M, Gores GJ (2004) Lysosomes in cell death. Oncogene 23:2881–2890

    CAS  PubMed  Google Scholar 

  • Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA Jr (1998) The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA 95:11140–11145

    CAS  PubMed  Google Scholar 

  • Hahn GM (1979) Potential for therapy of drugs and hyperthermia. Cancer Res 39:2264–2268

    CAS  PubMed  Google Scholar 

  • Hall EJ (2000) Radiobiology for the radiologist, 5th edn. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  • Huang L-C, Clarkin KC, Wahl GM (1996) Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc Natl Acad Sci USA 93:4827–4832

    CAS  PubMed  Google Scholar 

  • Huang G, Chen H, Dong Y, Luo X, Yu H, Moore Z, Bey EA, Boothman DA, Gao J (2013) Superparamagnetic iron oxide nanoparticles: amplifying ROS stress to improve anticancer drug efficacy. Theranostics 3:116–126

    CAS  PubMed Central  PubMed  Google Scholar 

  • Izumi T, Wiederhold LR, Roy G, Roy R, Jaiswal A, Bhakat KK, Mitra S, Hazra TK (2003) Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage. Toxicology 193:43–65

    CAS  PubMed  Google Scholar 

  • Jackson SP (2002) Sensing and repairing DNA double-strand breaks. Carcinogenesis 23:687–696

    CAS  PubMed  Google Scholar 

  • Jia L, Kelsey SM, Grahn MF, Jiang XR, Newland AC (1996) Increased activity and sensitivity of mitochondrial respiratory enzymes to TNFα-mediated inhibition is associated with cytotoxicity in drug-resistant leukemic cell lines. Blood 87:2401–2410

    CAS  PubMed  Google Scholar 

  • Jia L, Allen PD, Macey MG, Grahn MF, Newland AC, Kelsey SM (1997) Mitochondrial electron transport chain activity, but not ATP synthesis, is required for drug-induced apoptosis in human leukaemic cells: a possible novel mechanism of regulating drug resistance. Br J Haematol 98:686–698

    CAS  PubMed  Google Scholar 

  • Joiner MC, Marples B, Lambin P, Short SC, Turesson I (2001) Low-dose hypersensitivity: current status and possible mechanisms. Int J Radiat Oncol Biol Phys 49:379–389

    CAS  PubMed  Google Scholar 

  • Kadhim MA, Moore SR, Goodwin EH (2004) Interrelationships amongst radiation-induced genomic instability, bystander effects, and the adaptive response. Mut Res/Fundam Mol Mech Mutagen 568:21–32

    CAS  Google Scholar 

  • Kern JC, Kehrer JP (2002) Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact 139:79–95

    CAS  PubMed  Google Scholar 

  • Kochi M, Takeuchi S, Mizutani T, Mochizuki K, Matsumoto Y, Saito Y (1980) Antitumor activity of benzaldehyde. Cancer Treat Rep 64:21–23

    CAS  PubMed  Google Scholar 

  • Kowaltowski AJ, Vercesi AE (1999) Mitochondrial damage induced by conditions of oxidative stress. Free Rad Biol Med 26:463–471

    CAS  PubMed  Google Scholar 

  • Kroemer G, Martin SJ (2005) Caspase-independent cell death. Nat Med 11:723–730

    Google Scholar 

  • Kundu JK, Surh Y-J (2008) Inflammation: gearing the journey to cancer. Mutat Res 659:15–30

    CAS  PubMed  Google Scholar 

  • Lambin P, Marples B, Fertil B, Malaise EP, Joiner MC (1993) Hypersensitivity of a human tumour cell line to very low dose radiation. Int J Radiat Biol 63:639–650

    CAS  PubMed  Google Scholar 

  • Lee YJ, Shacter E (2000) Hydrogen peroxide inhibits activation, not activity, of cellular caspase-3 in vivo. Free Radic Biol Med 29:684–692

    CAS  PubMed  Google Scholar 

  • Lobrich M, Rydberg B, Cooper PK (1995) Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends. Proc Natl Acad Sci USA 92:12050–12054

    CAS  PubMed  Google Scholar 

  • Löbrich M, Rief N, Kühne M, Heckmann M, Fleckenstein J, Rübe C, Uder M (2005) In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc Natl Acad Sci USA 102:8984–8989

    PubMed  Google Scholar 

  • Marples B, Joiner MC (1995) The Elimination of Low-Dose Hypersensitivity in Chinese Hamster V79-379A Cells by Pretreatment with X Rays or Hydrogen Peroxide. Radiat Res 141:160–169

    CAS  PubMed  Google Scholar 

  • Maxwell CA, Fleisch MC, Costes SV, Erickson AC, Boissière A, Gupta R, Ravani SA, Parvin B, Barcellos-Hoff MH (2008) Targeted and nontargeted effects of ionizing radiation that impact genomic instability. Cancer Res 68:8304–8311

    CAS  PubMed  Google Scholar 

  • Maynard S, Schurman SH, Harboe C, De Souza-Pinto NC, Bohr VA (2009) Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30:2–10

    CAS  PubMed  Google Scholar 

  • Morgan WF (2003) Non-targeted and delayed effects of exposure to ionizing radiation: I, radiation-induced genomic instability and bystander effects in vitro. Radiat Res 159:567–580

    CAS  PubMed  Google Scholar 

  • Mueller MM, Fusenig NE (2004) Friends or foes-bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849

    CAS  PubMed  Google Scholar 

  • Pledgie A, Huang Y, Hacker A, Zhang Z, Woster PM, Davidson NE, Casero RA Jr (2005) Spermine oxidase SMO(PAOh1), Not N1-acetylpolyamine oxidase PAO, is the primary source of cytotoxic H2O2 in polyamine analogue-treated human breast cancer cell lines. J Biol Chem 280:39843–39851

    CAS  PubMed  Google Scholar 

  • Polticelli F, Salvi D, Mariottini P, Amendola R, Cervelli M (2012) Molecular evolution of the polyamine oxidase gene family in metazoa. BMC Evol Biol 12:90

    CAS  PubMed Central  PubMed  Google Scholar 

  • Portess DI, Bauer G, Hill MA, O’Neill P (2007) Low dose irradiation of non-transformed cells stimulates the selective removal of pre-cancerous cells via intercellular induction of apoptosis. Cancer Res 67:1246–1253

    CAS  PubMed  Google Scholar 

  • Prise KM, Schettino G, Folkard M, Held KD (2005) New insights on cell death from radiation exposure. Lancet Oncol 6:520–528

    CAS  PubMed  Google Scholar 

  • Rajalakshmi S, Rao RM, Sarma DS (1980) Carcinogen-DNA interaction: differential effects of distamycin-a and spermine on the formation of 7-methylguanine in DNA by N-methyl-N-nitrosourea, methylmethanesulfonate, and dimethylsulfate. Teratog Carcinog Mutagen 1:97–104

    CAS  PubMed  Google Scholar 

  • Recommendations of the International Commission on Radiological Protection (2007) Annals of the ICRP. ICRP publication 103 37 (2–4). 2007. ISBN 978-0-7020-3048-2

  • Roh C, Yu D-Y, Kim I et al (2012) The biological response of spermidine induced by ionization radiation. Molecules 17:145–150

    CAS  Google Scholar 

  • Schiller M, Blank N, Heyder P, Herrmann M, Gaipl US, Kalden JR, Lorenz HM (2005) Induction of apoptosis by spermine-metabolites in primary human blood cells and various tumor cell lines. Apoptosis 10:1151–1162

    CAS  PubMed  Google Scholar 

  • Schumacker PT (2006) Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 10:175–176

    CAS  PubMed  Google Scholar 

  • Seeberg E, Eide L, Bjørås M (1995) The base excision repair pathway. Trends Biochem Sci 20:391–397

    CAS  PubMed  Google Scholar 

  • Seiler N, Raul F (2005) Polyamines and apoptosis. J Cell Mol Med 9:623–642

    CAS  PubMed  Google Scholar 

  • Seril DN, Liao J, Yang GY, Yang CS (2003) Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis 24:353–362

    CAS  PubMed  Google Scholar 

  • Skarsgard LD, Harrison I, Durand RE (1991) The radiation response of asynchronous cells at low dose: evidence of substructure. Radiat Res 127:248–256

    CAS  PubMed  Google Scholar 

  • Skarsgard LD, Skwarchuk MW, Wouters BG (1994) The survival of asynchronousV79 cells at low radiation doses: modeling the response of mixed cell populations. Radiat Res 138:S72–S75

    CAS  PubMed  Google Scholar 

  • Soares FA, Shaughnessy SG, MacLarkey WR, Orr FW (1994) Quantification and morphologic demonstration of reactive oxygen species produced by Walker 256 tumor cells in vitro and during metastasis in vivo. Lab Invest 71:480–489

    CAS  PubMed  Google Scholar 

  • Sohal RS (1997) Mitochondria generate superoxide anion radicals and hydrogen peroxide. FASEB J 11:1269–1270

    CAS  PubMed  Google Scholar 

  • Stoka V, Turk B, Turk V (2005) Lysosomal cysteine proteinases: structural features and their role in apoptosis. IUBMB Life 57:347–353

    CAS  PubMed  Google Scholar 

  • Sykes PJ, Day TK, Swinburne SJ, Lane JM, Morley AA, Hooker AM, Bhat M (2006) In Vivo mutagenic effect of very low dose radiation. Dose-Response 4:309–316

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takahashi T, Horie H, Kojima O, Itoh M (1993) Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil suppositories for patients with rectal cancer. Jpn J Surg 23:1043–1048

    CAS  Google Scholar 

  • Teramoto S, Tomita T, Matsui H, Ohga E, Matsuse T, Ouchi Y (1999) Hydrogen peroxide-induced apoptosis and necrosis in human lung fibroblasts: protective roles of glutathione. Jpn J Pharmacol 79:33–40

    CAS  PubMed  Google Scholar 

  • Thompson LH, Brookman KW, Dillehay LE, Carrano AV, Mazrimas JA, Mooney CL, Minkler JL (1982) A CHO-cell strain having hypersensitivity to mutagens, a defect in DNA strand-break repair, and an extraordinary baseline frequency of sister-chromatid exchange. Mutat Res 95:427–440

    CAS  PubMed  Google Scholar 

  • Thompson LH, Salazar EP, Brookman KW, Collins CC, Stewart SA, Busch DB, Weber CA (1987) Recent progress with the DNA repair mutants of Chinese hamster ovary cells. J Cell Sci Suppl 6:97–110

    CAS  PubMed  Google Scholar 

  • Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579–591

    CAS  PubMed  Google Scholar 

  • Van Der Zee J (2002) Heating the patient: a promising approach? Ann Oncol 13:1173–1184

    PubMed  Google Scholar 

  • Vernon CC, Hand JW, Field SB, Machin D, Whaley JB, Van der Zee J, Van Putten WL, Van Rhoon GC, Van Dijk JD, Gonzalez D, Liu FF, Goodman P, Sherar M, International Collaborative Hyperthermia Group (1996) Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. Int J Radiat Oncol Biol Phys 35:731–744

    CAS  PubMed  Google Scholar 

  • Vujcic S, Diegelman P, Bacchi CJ, Kramer DL, Porter CW (2002) Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem J 367:665–675

    CAS  PubMed  Google Scholar 

  • Wallace HM, Fraser AV (2004) Inhibitors of polyamine metabolism: review article. Amino Acids 26:353–365

    CAS  PubMed  Google Scholar 

  • Wallace HM, Duthie J, Evans DM, Lamond S, Nicoll KM, Heys SD (2000) Alterations in polyamine catabolic enzymes in human breast cancer tissue. Clin Cancer Res 6:3657–3661

    CAS  PubMed  Google Scholar 

  • Ward JF (1998) Nature of lesions formed by ionising radiation. In: Nickoloff JA, Hoekstra MF (eds) DNA damage and repair: DNA repair in higher eukaryotes. Humana Press, Totowa, pp 65–84

    Google Scholar 

  • Wolff S (1998) The adaptive response in radiobiology: evolving insights and implications. Environ Health Perspect 106:277–283

    PubMed Central  PubMed  Google Scholar 

  • Wouters BG, Skarsgard LD (1994) The response of a human tumor cell line to low radiation doses: evidence of enhanced sensitivity. Radiat Res 138:S76–S80

    CAS  PubMed  Google Scholar 

  • Wright EG, Coates PJ (2006) Untargeted effects of ionizing radiation: implications for radiation pathology. Mutat Res 597:119–132

    CAS  PubMed  Google Scholar 

  • Xu H, Chaturvedi R, Cheng Y, Bussiere FI, Asim M, Yao MD, Potosky D, Meltzer SJ, Rhee JG, Kim SS, Moss SF, Hacker A, Wang Y, Casero RA Jr, Wilson KT (2004) Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res 64:8521–8525

    CAS  PubMed  Google Scholar 

  • Yoshikawa T, Kokura S, Tanaka K, Naito T, Kondo M (1995) A novel cancer therapy based on oxygen radicals. Cancer Res 55:1617–1620

    CAS  PubMed  Google Scholar 

  • Zastawny TH, Czerwinska B, Drzewiecka B, Olinski R (1997) Radiation-induced oxidative DNA base damage and its repair in nuclear matrix-associated DNA and in bulk DNA in hepatic chromatin of rat upon whole-body gamma-irradiation. Free Radical Biol Med 22:101–107

    CAS  Google Scholar 

  • Zdolsek J, Zhang H, Roberg K, Brunk UT (1993) H2O2-mediated damage to lysosomal membranes of J-774 cells. Free Radic Res Commun 18:71–85

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was funded in part by the Italian MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca), by MIUR-PRIN (Cofin), by Istituto Superiore di Sanità “Project Italy-USA” and by Istituto Pasteur Fondazione Cenci Bolognetti (EA). Thanks are due to “Fondazione Sovena” for the scholarship given to Dr. Giampiero Tempera for supporting his postdoc.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. UT BIORAD RAB, CR Casaccia, ENEA, 00123, Rome, Italy

    Roberto Amendola & Emiliano Fratini

  2. Department of Biology, University of “Roma Tre”, 00146, Rome, Italy

    Manuela Cervelli & Paolo Mariottini

  3. Istituto Pasteur Fondazione Cenci Bolognetti and Department of Biochemical Sciences ‘A. Rossi Fanelli’, SAPIENZA University of Rome and CNR, Biology and Molecular Pathology Institutes, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Giampiero Tempera & Enzo Agostinelli

  4. Laboratory of Molecular Biology, G. Gaslini Institute, Via G. Gaslini, 16147, Genoa, Italy

    Luigi Varesio

Authors
  1. Roberto Amendola
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  2. Manuela Cervelli
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  3. Giampiero Tempera
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  4. Emiliano Fratini
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  5. Luigi Varesio
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  6. Paolo Mariottini
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  7. Enzo Agostinelli
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Corresponding author

Correspondence to Roberto Amendola.

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Amendola, R., Cervelli, M., Tempera, G. et al. Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response. Amino Acids 46, 487–498 (2014). https://doi.org/10.1007/s00726-013-1579-9

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  • DOI: https://doi.org/10.1007/s00726-013-1579-9

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