Biopolym. Cell. 2017; 33(1):24-33.
http://dx.doi.org/10.7124/bc.000941
Мініогляди
Експериментальні та популяційні дослідження рівня пошкоджень ДНК e здорових організмах
1, 2Сьяксте Н.
  1. Інститут біології
    Латвійський університет
    вул. Мієр 3, Саласпилс, Латвія, LV-2169
  2. Медичний факультет,
    Латвійський університет
    вул. Шарлотес 1а, Рига, Латвія, LV-1001

Abstract

Пошкодження ДНК є інформативним біомаркером для молекулярної епідеміології, так як вони пов'язані з багатьма захворюваннями людини. У той же час рівень пошкоджень ДНК може залежати від внутрішніх властивостей притаманних здоровим людям: спадковості, статі, віку і статури. Метою даного огляду є узагальнення даних щодо розривів ДНК у здорових людей в залежності від їхніх характеристик у порівняння з даними експериментів і спостережень за тваринами. У лабораторних тварин кількох ліній спостерігають підвищений рівень розривів ДНК, у людини - кілька генних поліморфізмів асоційовані з підвищеним рівнем розривів, але вважається, що визначальними є зовнішні фактори. У самців тварин ДНК пошкоджена сильніше, ніж у самиць, дані по людині суперечливі і залежать від раси. Експериментальні моделі показують підвищений рівень одно- і дволанцюгових розривів ДНК при ожирінні. Дані досліджень на людині менш переконливі, краще відтворюються дані щодо підвищеного рівеня дволанцюгових розривів ДНК у людей із зайвою вагою. По одноланцюгових розривах ДНК при старінні дані суперечливі, переконливо показано зростання дволанцюгових розривів ДНК з віком.
Keywords: розриви ДНК, старіння, стать, ожиріння
Повний текст: (PDF, англійською)

References

[1] Magnander K, Elmroth K. Biological consequences of formation and repair of complex DNA damage. Cancer Lett. 2012;327(1-2):90-6.
[2] Stone MP, Huang H, Brown KL, Shanmugam G. Chemistry and structural biology of DNA damage and biological consequences. Chem Biodivers. 2011;8(9):1571-615.
[3] Selvaraju V, Joshi M, Suresh S, Sanchez JA, Maulik N, Maulik G. Diabetes, oxidative stress, molecular mechanism, and cardiovascular disease--an overview. Toxicol Mech Methods. 2012;22(5):330-5.
[4] Supriya Simon A, Dinesh Roy D, Jayapal V, Vijayakumar T. Somatic DNA damages in cardiovascular autonomic neuropathy. Indian J Clin Biochem. 2011;26(1):50-6.
[5] Milic M, Frustaci A, Del Bufalo A, Sánchez-Alarcón J, Valencia-Quintana R, Russo P, Bonassi S. DNA damage in non-communicable diseases: A clinical and epidemiological perspective. Mutat Res. 2015;776:118-27.
[6] Algire C, Moiseeva O, Deschênes-Simard X, Amrein L, Petruccelli L, Birman E, Viollet B, Ferbeyre G, Pollak MN. Metformin reduces endogenous reactive oxygen species and associated DNA damage. Cancer Prev Res (Phila). 2012;5(4):536-43.
[7] Aziz K, Nowsheen S, Pantelias G, Iliakis G, Gorgoulis VG, Georgakilas AG. Targeting DNA damage and repair: embracing the pharmacological era for successful cancer therapy. Pharmacol Ther. 2012;133(3):334-50.
[8] Sjakste N, Sjakste T. Possible involvement of DNA strand breaks in regulation of cell differentiation. Eur J Histochem. 2007;51(2):81-94.
[9] Sjakste NI, Sjakste TG. Possible involvement of DNA breaks in epigenetic regulation of cell differentiation. Rus J Genet. 2007; 43(5):467–84.
[10] Sjakste TG, Lilp IG, Sjakste TG. Chromosomal aberrations and molecular weight of single – stranded DNA fragments in embryonic fibroblasts of 101. H and CBA mice. Bull Exp Biol Med. 1981; 92(3):1231-3.
[11] Tronov VA, Grin'ko EV, Afanas'ev GG, Filippovich IV. [Study of DNA damage and heterogeneity of cells by a gel microelectrophoresis method]. Biofizika. 1994;39(5):810-9.
[12] Smith TB, De Iuliis GN, Lord T, Aitken RJ. The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line. Reproduction. 2013;146(3):253-62.
[13] Reliene R, Yamamoto ML, Rao PN, Schiestl RH. Genomic instability in mice is greater in Fanconi anemia caused by deficiency of Fancd2 than Fancg. Cancer Res. 2010;70(23):9703-10.
[14] Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang XM, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E. Lack of p21 expression links cell cycle control and appendage regeneration in mice. Proc Natl Acad Sci U S A. 2010;107(13):5845-50.
[15] Kahan V, Ribeiro DA, Andersen ML, Alvarenga TA, Tufik S. Sleep loss induces differential response related to genotoxicity in multiple organs of three different mice strains. Basic Clin Pharmacol Toxicol. 2010;107(1):598-602.
[16] Watters JL, Satia JA, Kupper LL, Swenberg JA, Schroeder JC, Switzer BR. Associations of antioxidant nutrients and oxidative DNA damage in healthy African-American and White adults. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1428-36.
[17] Slyskova J, Naccarati A, Polakova V, Pardini B, Vodickova L, Stetina R, Schmuczerova J, Smerhovsky Z, Lipska L, Vodicka P. DNA damage and nucleotide excision repair capacity in healthy individuals. Environ Mol Mutagen. 2011;52(7):511-7.
[18] Slyskova J, Lorenzo Y, Karlsen A, Carlsen MH, Novosadova V, Blomhoff R, Vodicka P, Collins AR. Both genetic and dietary factors underlie individual differences in DNA damage levels and DNA repair capacity. DNA Repair (Amst). 2014;16:66-73.
[19] Garm C, Moreno-Villanueva M, Bürkle A, Larsen LA, Bohr VA, Christensen K, Stevnsner T. Genetic and environmental influence on DNA strand break repair: a twin study. Environ Mol Mutagen. 2013;54(6):414-20.
[20] Noschang CG, Pettenuzzo LF, von Pozzer Toigo E, Andreazza AC, Krolow R, Fachin A, Avila MC, Arcego D, Crema LM, Diehl LA, Gonçalvez CA, Vendite D, Dalmaz C. Sex-specific differences on caffeine consumption and chronic stress-induced anxiety-like behavior and DNA breaks in the hippocampus. Pharmacol Biochem Behav. 2009;94(1):63-9.
[21] Noschang CG, Krolow R, Fontella FU, Arcego DM, Diehl LA, Weis SN, Arteni NS, Dalmaz C. Neonatal handling impairs spatial memory and leads to altered nitric oxide production and DNA breaks in a sex specific manner. Neurochem Res. 2010;35(7):1083-91.
[22] Akcha F, Leday G, Pfohl-Leszkowicz A. Measurement of DNA adducts and strand breaks in dab (Limanda limanda) collected in the field: effects of biotic (age, sex) and abiotic (sampling site and period) factors on the extent of DNA damage. Mutat Res. 2004;552(1-2):197-207.
[23] Scheirs J, De Coen A, Covaci A, Beernaert J, Kayawe VM, Caturla M, De Wolf H, Baert P, Van Oostveldt P, Verhagen R, Blust R, De Coen W. Genotoxicity in wood mice (Apodemus sylvaticus) along a pollution gradient: exposure-, age-, and gender-related effects. Environ Toxicol Chem. 2006;25(8):2154-62.
[24] Hofer T, Karlsson HL, Möller L. DNA oxidative damage and strand breaks in young healthy individuals: a gender difference and the role of life style factors. Free Radic Res. 2006;40(7):707-14.
[25] Trzeciak AR, Barnes J, Ejiogu N, Foster K, Brant LJ, Zonderman AB, Evans MK. Age, sex, and race influence single-strand break repair capacity in a human population. Free Radic Biol Med. 2008;45(12):1631-41.
[26] Molz P, Ellwanger JH, Zenkner FF, Campos D, Prá D, Putzke MT, Franke SI. Recognition memory and DNA damage in undernourished young rats. An Acad Bras Cienc. 2016;88(3 Suppl):1863-73.
[27] Bankoglu EE, Seyfried F, Rotzinger L, Nordbeck A, Corteville C, Jurowich C, Germer CT, Otto C, Stopper H. Impact of weight loss induced by gastric bypass or caloric restriction on oxidative stress and genomic damage in obese Zucker rats. Free Radic Biol Med. 2016;94:208-17.
[28] Vendramini V, Cedenho AP, Miraglia SM, Spaine DM. Reproductive function of the male obese Zucker rats: alteration in sperm production and sperm DNA damage. Reprod Sci. 2014;21(2):221-9.
[29] Duale N, Steffensen IL, Andersen J, Brevik A, Brunborg G, Lindeman B. Impaired sperm chromatin integrity in obese mice. Andrology. 2014;2(2):234-43.
[30] Larcombe SD, Tregaskes CA, Coffey J, Stevenson AE, Alexander LG, Arnold KE. Oxidative stress, activity behaviour and body mass in captive parrots. Conserv Physiol. 2015;3(1):cov045.
[31] Vares G, Wang B, Ishii-Ohba H, Nenoi M, Nakajima T. Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice. PLoS One. 2014;9(8):e106277.
[32] Løhr M, Folkmann JK, Sheykhzade M, Jensen LJ, Kermanizadeh A, Loft S, Møller P. Hepatic oxidative stress, genotoxicity and vascular dysfunction in lean or obese Zucker rats. PLoS One. 2015;10(3):e0118773.
[33] Sampath H, Vartanian V, Rollins MR, Sakumi K, Nakabeppu Y, Lloyd RS. 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PLoS One. 2012;7(12):e51697.
[34] Wang J, Luo X, Xu B, Wei J, Zhang Z, Zhu H. Elevated oxidative damage in kitchen workers in Chinese restaurants. J Occup Health. 2011;53(5):327-33.
[35] Jones DA, Prior SL, Barry JD, Caplin S, Baxter JN, Stephens JW. Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes. Diabetes Res Clin Pract. 2014;106(3):627-33.
[36] Wallner M, Antl N, Rittmannsberger B, Schreidl S, Najafi K, Müllner E, Mölzer C, Ferk F, Knasmüller S, Marculescu R, Doberer D, Poulsen HE, Vitek L, Bulmer AC, Wagner KH. Anti-genotoxic potential of bilirubin in vivo: damage to DNA in hyperbilirubinemic human and animal models. Cancer Prev Res (Phila). 2013;6(10):1056-63.
[37] Donmez-Altuntas H, Sahin F, Bayram F, Bitgen N, Mert M, Guclu K, Hamurcu Z, Arıbas S, Gundogan K, Diri H. Evaluation of chromosomal damage, cytostasis, cytotoxicity, oxidative DNA damage and their association with body-mass index in obese subjects. Mutat Res Genet Toxicol Environ Mutagen. 2014;771:30-6.
[38] Milić M, Kišan M, Rogulj D, Radman M, Lovrenčić MV, Konjevoda P, Domijan AM. Level of primary DNA damage in the early stage of metabolic syndrome. Mutat Res. 2013;758(1-2):1-5.
[39] Karaman A, Aydın H, Geçkinli B, Çetinkaya A, Karaman S. DNA damage is increased in lymphocytes of patients with metabolic syndrome. Mutat Res Genet Toxicol Environ Mutagen. 2015;782:30-5.
[40] Karbownik-Lewinska M, Szosland J, Kokoszko-Bilska A, Stępniak J, Zasada K, Gesing A, Lewinski A. Direct contribution of obesity to oxidative damage to macromolecules. Neuro Endocrinol Lett. 2012;33(4):453-61.
[41] Habermann N, Makar KW, Abbenhardt C, Xiao L, Wang CY, Utsugi HK, Alfano CM, Campbell KL, Duggan C, Foster-Schubert KE, Mason CE, Imayama I, Blackburn GL, Potter JD, McTiernan A, Ulrich CM. No effect of caloric restriction or exercise on radiation repair capacity. Med Sci Sports Exerc. 2015;47(5):896-904.
[42] Ibero-Baraibar I, Azqueta A, Lopez de Cerain A, Martinez JA, Zulet MA. Assessment of DNA damage using comet assay in middle-aged overweight/obese subjects after following a hypocaloric diet supplemented with cocoa extract. Mutagenesis. 2015;30(1):139-46.
[43] Azzarà A, Pirillo C, Giovannini C, Federico G, Scarpato R. Different repair kinetic of DSBs induced by mitomycin C in peripheral lymphocytes of obese and normal weight adolescents. Mutat Res. 2016;789:9-14.
[44] Dupont C, Faure C, Sermondade N, Boubaya M, Eustache F, Clément P, Briot P, Berthaut I, Levy V, Cedrin-Durnerin I, Benzacken B, Chavatte-Palmer P, Levy R. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl. 2013;15(5):622-5.
[45] Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GM. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod. 2014;29(2):193-200.
[46] Heuser VD, de Andrade VM, Peres A, Gomes de Macedo Braga LM, Bogo Chies JA. Influence of age and sex on the spontaneous DNA damage detected by micronucleus test and comet assay in mice peripheral blood cells. Cell Biol Int. 2008;32(10):1223-9.
[47] Bhilwade HN, Jayakumar S, Chaubey RC. Age-dependent changes in spontaneous frequency of micronucleated erythrocytes in bone marrow and DNA damage in peripheral blood of Swiss mice. Mutat Res Genet Toxicol Environ Mutagen. 2014;770:80-4.
[48] Sreedhar R, Giridharan VV, Arumugam S, Karuppagounder V, Palaniyandi SS, Krishnamurthy P, Quevedo J, Watanabe K, Konishi T, Thandavarayan RA. Role of MAPK-mediated endoplasmic reticulum stress signaling in the heart during aging in senescence-accelerated prone mice. Biofactors. 2016;42(4):368-75.
[49] Hayashi M, Nishida K, Endoh D, Okui T. Production of age-related DNA strand breakage in brain cells of senescence-accelerated prone (SAMP1) mouse. Exp Anim. 2003;52(4):353-7.
[50] Tonini CL, Campagnaro BP, Louro LP, Pereira TM, Vasquez EC, Meyrelles SS. Effects of Aging and Hypercholesterolemia on Oxidative Stress and DNA Damage in Bone Marrow Mononuclear Cells in Apolipoprotein E-deficient Mice. Int J Mol Sci. 2013;14(2):3325-42.
[51] Beerman I, Seita J, Inlay MA, Weissman IL, Rossi DJ. Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle. Cell Stem Cell. 2014;15(1):37-50.
[52] Folkmann JK, Loft S, Møller P. Oxidatively damaged DNA in aging dyslipidemic ApoE-/- and wild-type mice. Mutagenesis. 2007;22(2):105-10.
[53] López-Diazguerrero NE, Luna-López A, Gutiérrez-Ruiz MC, Zentella A, Königsberg M. Susceptibility of DNA to oxidative stressors in young and aging mice. Life Sci. 2005;77(22):2840-54.
[54] Guo ZM, Yang H, Hamilton ML, VanRemmen H, Richardson A. Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta. Mech Ageing Dev. 2001;122(15):1771-86.
[55] Sivonová M, Tatarková Z, Duracková Z, Dobrota D, Lehotský J, Matáková T, Kaplán P. Relationship between antioxidant potential and oxidative damage to lipids, proteins and DNA in aged rats. Physiol Res. 2007;56(6):757-64.
[56] Gedik CM, Grant G, Morrice PC, Wood SG, Collins AR. Effects of age and dietary restriction on oxidative DNA damage, antioxidant protection and DNA repair in rats. Eur J Nutr. 2005;44(5):263-72.
[57] Sahhugi Z, Hasenan SM, Jubri Z. Protective effects of gelam honey against oxidative damage in young and aged rats. Oxid Med Cell Longev. 2014;2014:673628.
[58] Jubri Z, Rahim NB, Aan GJ. Manuka honey protects middle-aged rats from oxidative damage. Clinics (Sao Paulo). 2013;68(11):1446-54.
[59] El-Sayyad HI, Khalifa SA, El-Sayyad FI, Al-Gebaly AS, El-Mansy AA, Mohammed EA. Aging-related changes of optic nerve of Wistar albino rats. Age (Dordr). 2014;36(2):519-32.
[60] Swain U, Subba Rao K. Study of DNA damage via the comet assay and base excision repair activities in rat brain neurons and astrocytes during aging. Mech Ageing Dev. 2011;132(8-9):374-81.
[61] Hashimoto K, Takasaki W, Yamoto T, Manabe S, Sato I, Tsuda S. Effect of glutathione (GSH) depletion on DNA damage and blood chemistry in aged and young rats. J Toxicol Sci. 2008;33(4):421-9.
[62] Hashimoto K, Takasaki W, Sato I, Tsuda S. DNA damage measured by comet assay and 8-OH-dG formation related to blood chemical analyses in aged rats. J Toxicol Sci. 2007;32(3):249-59.
[63] Velegzhaninov I, Mezenceva V, Shostal O, Baranova A, Moskalev A. Age dynamics of DNA damage and CpG methylation in the peripheral blood leukocytes of mice. Mutat Res. 2015;775:38-42.
[64] White RR, Vijg J. Do DNA Double-Strand Breaks Drive Aging? Mol Cell. 2016;63(5):729-38.
[65] Lenart P, Bienertová-Vašků J. Double strand breaks may be a missing link between entropy and aging. Mech Ageing Dev. 2016;157:1-6.
[66] Gorbunova V, Seluanov A. DNA double strand break repair, aging and the chromatin connection. Mutat Res. 2016;788:2-6.
[67] Li Z, Zhang W, Chen Y, Guo W, Zhang J, Tang H, Xu Z, Zhang H, Tao Y, Wang F, Jiang Y, Sun FL, Mao Z. Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans. Cell Death Differ. 2016;23(11):1765-1777.
[68] MacRae SL, Croken MM, Calder RB, Aliper A, Milholland B, White RR, Zhavoronkov A, Gladyshev VN, Seluanov A, Gorbunova V, Zhang ZD, Vijg J. DNA repair in species with extreme lifespan differences. Aging (Albany NY). 2015;7(12):1171-84.
[69] White RR, Milholland B, de Bruin A, Curran S, Laberge RM, van Steeg H, Campisi J, Maslov AY, Vijg J. Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing. Nat Commun. 2015;6:6790.
[70] Petrova NV, Luzhin AV, Serebrovskaya EO, Ryumina AP, Velichko AK, Razin SV, Kantidze OL. Inducing cellular senescence in vitro by using genetically encoded photosensitizers. Aging (Albany NY). 2016;8(10):2449-2462.
[71] Velichko AK, Petrova NV, Razin SV, Kantidze OL. Mechanism of heat stress-induced cellular senescence elucidates the exclusive vulnerability of early S-phase cells to mild genotoxic stress. Nucleic Acids Res. 2015;43(13):6309-20.
[72] Collins AR, Azqueta A. DNA repair as a biomarker in human biomonitoring studies; further applications of the comet assay. Mutat Res. 2012;736(1-2):122-9.
[73] Lenart P, Krejci L. DNA, the central molecule of aging. Mutat Res. 2016;786:1-7.
[74] Sharma PM, Ponnaiya B, Taveras M, Shuryak I, Turner H, Brenner DJ. High throughput measurement of γH2AX DSB repair kinetics in a healthy human population. PLoS One. 2015;10(3):e0121083.
[75] Løhr M, Jensen A, Eriksen L, Grønbæk M, Loft S, Møller P. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells. Oncotarget. 2015;6(5):2641-53.