Nanoteknolojiden nanogenotoksikolojiye: kobalt-krom nanopartiküllerinin genotoksik etkisi

Öz

Nanoteknoloji materyalleri nanometre seviyesinde ölçülebilecek düzeyde işleyen, pek çok araştırma alanını ya da disiplini birleştiren multidisipliner bir teknolojidir. Nanomateryaller; bilim, teknoloji, iletişim, elektronik, endüstri, eczacılık, tıp, çevre, tüketici ürünleri ve askeri alanlarda yaygın şekilde kullanılmaktadır. Son zamanlara kadar nanomateryallerin insan sağlığı ve çevre üzerinde toksik ya da tehlikeli etkilere sahip olup olmadıkları hakkında çok az şey bilinmekteydi. Ancak çeşitli çalışmalar bazı nanomateryallere örneğin nanopartiküllere maruz kalmanın insanlarda ve hayvanlarda bazı olumsuz etkilere yol açabileceğini göstermiştir. Son yıllarda nanotoksikoloji konusuna yapılan yayınların sayısındaki nanomateryallerin genotoksisitesi hakkında hala bir boşluk bulunmaktadır. Üstün mekanik özelliklere sahip metal nanopartiküller ve alaşımları, iskelet-kas sisteminin mekanik koşullarına kolaylıkla uyum gösterebilen malzemelerdir. Kobaltkrom alaşımları eklem protezi ve kemik yenileme malzemesi olarak ortopedik uygulamalarda, çene cerrahisinde dolgularda ve diş implantlarında, kalp damar cerrahisinde özellikle stent uygulamalarında yaygın bir şekilde kullanılmaktadırlar. Metal nanopartiküllerin insan üzerindeki sitotoksisite ve genotoksisitesi ile ilgili çalışmalar, bazı metal nanopartiküllerin sitotoksik ve genotoksik etkilere sahip olduğu ve insanlar için tehlikeli olabileceklerini göstermiştir. Fakat kobalt krom nanopartiküllerin genotoksik etkileri hakkında az sayıda çalışma rapor edilmiştir. Bu çalışmalardan elde edilen bilgiler, kobalt-krom nanopartiküllerinin sitotoksik ve genotoksik etkiye sahip olduğunu göstermiştir. Protezleri kobalt-kromdan yapılmış bulunan hastalarda, protezlerin aşınması sonucu oluşan kalıntıların DNA ve kromozom hasarına neden olduğu belirtilmiştir. Ayrıca kalça protezi uygulamasından sonra bu tip hastaların; mesane, üreter, böbrek ve prostat gibi üriner sistem kanserleri bakımından normal populasyona göre yüksek risk taşıdıkları da bulunmuştur. Nanopartiküllerin uzun dönem etkileri hakkındaki biyouyumluluk ve toksisite testlerinin sınırlı olmasından ve nanogenotoksisiteye odaklanan az sayıda araştırma bulunmasından dolayı, nanopartiküllerin hücrelerdeki özellikle genetik materyal üzerindeki etki mekanizmaları henüz detaylı olarak açıklığa kavuşturulamamıştır. Bu nedenle nanopartiküllerin epigenetik etkileri ve nanopartikül tarafından indüklenen genotoksik olayların mekanizmasını anlamak için, hücre döngüsü ve DNA onarımını kapsayan iyi tasarlanmış çalışmaların yapılması gerekmektedir. Bu sayede gelecekte nanomateryallerin biyouyumluluklarının sağlanması, sağlık için zararlı etkilerinin en aza indirilmesi ve bilinçli tasarımların yapılmasını sağlayacak bilgiye sahip olabiliriz

Anahtar Kelimeler

• Nanomateryaller, metal nanopartiküller, krom-kobalt alaşımı, genotoksisite

From nanotechnology to nanogenotoxicology: genotoxic effect of cobalt-chromium nanoparticles

Öz

Nanotechnology is a multi-disciplinary technology that processes the materials that can be measured at nanometer-level and combines many research fields and disciplines. Nanomaterials NMs are widely used in the fields of science, technology, communication, electronics, industry, pharmacy, medicine, environment, consumer products and the military. Until recently little has been known about whether or not nanomaterials have a toxic or hazardous effects on human health and the environment. However, several studies have indicated that exposure to some nanomaterials, e.g. nanoparticles, can cause some adverse effects in humans and animals. Over the last years the number of publications focusing on nanotoxicology has gained momentum, but, there is still a gap about the genotoxicity of nanomaterials. Metal nanoparticles and their alloys with excellent mechanical properties are the materials which can be easily adapted to the mechanical conditions of the musculoskeletal system. Cobalt-chromium alloys are widely used in orthopedic applications as joint prosthesis and bone regeneration material, fillings and dental implants in jaw surgery, and in cardiovascular surgery, especially stent applications. Studies about cytotoxicity and genotoxicity of metal nanoparticles on human indicate that some metal nanoparticles have cytotoxic and genotoxic effects and they may be hazardous for humans. However, a few studies have been reported concerning the genotoxic effects of cobalt-chromium nanoparticles. The data from these studies indicate that cobalt-chromium nanoparticles have cytotoxic and genotoxic effects. It has been stated that the wear debris from implants cause DNA and chromosome damage in patients with cobalt-chromium replacements. It was also found that the risk of urinary cancers such as bladder, ureter, kidney and prostate in patients after hip replacement was higher than among the wider population. Because there are few biocompatibility and toxicity tests on the long-term effects of nanoparticles and limited amount of research focused on nanogenotoxicity, the effect mechanisms of nanoparticles on cells, especially genetic material, are not yet elucidated in detail. For this reason the well designed experiments including cell-cycle and DNA repair are required to understand the epigenetic effects of nanoparticles and mechanisms of nanoparticle-induced genotoxic events. Thus we may have information that will allow making informed designs, ensuring biocompatibility of nanomaterials and minimising their adverse effects for health in the future.

Anahtar Kelimeler

• Nanomaterials, metal nanoparticles, cobalt-chromium alloy, genotoxicity

Kaynakça

1. 1. Thrall JH. Nanotechnology and medicine. Radiology, 2004; 230: 315-8.
2. 2. Kuzma J, Priest S. Nanotechnology, risk, and oversight: learning lessons from related emerging technologies. 2010; Risk Anal, 30 (11): 1688-98.
3. 3. Gupta J. Nanotechnology applications in medicine and dentistry. J Investig Clin Dent, 2011; 2: 81-8.
4. 4. Syed S, Zubair A, Frieri M. Immune response to nanomaterials: implications for medicine and literature review. Curr Allergy Asthm Rep, 2013; 13 (1): 50-7.
5. 5. Gök H. Fiziksel tıp ve rehabilitasyon uzmanlarının nanoteknolojiden beklentileri. Türk Fiz Tıp Rehabilitasyon Derg, 2007; 53 (2): 13-7.
6. 6. Drexler KE. Nanotechnology: from Feynman to Funding. Bull Sci Technol Soc, 2004; 24 (1): 21-7. 7. Kocaefe Ç. NANOTIP: Yaşam bilimlerinde nanoteknoloji uygulamaları. Hacettepe Tıp Derg, 2007; 38: 33-8.
7. 8. Fu L, Cao L, Liu Y, Daoban Z. Molecular and nanoscale materials and devices in electronics. Adv Colloid Interface Sci, 2004; 111: 133–57.
8. 9. http://www.tubitak.gov.tr/tubitak_content_files/ vizyon, 2023 (14.02.2012).

9. 10. Koch CC. Nanostructed materials processing, properties, and applications. 2nd ed. New York: William Andrew, 2000.
10. 11. Singh N, Manshian B, Jenkins GJS, Griffiths SM, Williams PM, Maffeis TGG, et al. Nanogenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials, 2009; 30 (23-24): 3891–914.
11. 12. Doak SH, Griffiths SM, Manshian B, Singh N, Williams PM, Brown AP, et al. Confounding experimental considerations in nanogenotoxicology. Mutagenesis, 2009; 24 (4): 285-93.
12. 13. Conti J, Satterfield T, Harthorn BH. Vulnerability and social justice as factors in emergent US. nanotechnology risk perceptions. Risk Anal, 2011; 31 (11): 1734-48.
13. 14. Khare P, Sonane M, Pandey R, Ali S, Gupta KC, Satish A. Adverse effects of TiO2 and ZnO nanoparticles in soil nematode, Caenorhabditis elegans. J Biomed Nanotechnol, 2011; 7 (1): 116-7.
14. 15. Al-Subiai SN, Arlt VM, Frickers PE, Readman JW, Stolpe B, Lead JR, et al. Merging nanogenotoxicology with eco-genotoxicology: an integrated approach to determine interactive genotoxic and sub-lethal toxic effects of C60 fullerenes and fluoranthene in marine mussels, Mytilus sp. Mutat Res, 2012; 745(1-2): 92-103.
15. 16. Freitas RA. What is nanomedicine? Nanomedicine, 2005; 1(1): 2-9.
16. 17. Yula E, Deveci Ö. Nanotıp, mikrodizilimler ve klinik mikrobiyolojide kullanımları. Dicle Tıp Derg, 2010; 37 (4): 422-8.
17. 18. Tomalia DA, Reyna LA, Svenson S. Dendrimers as multipurpose nanodevices for oncology drug delivery and diagnostic imaging. Biochem Soc Trans, 2007; 35: 61-7.
18. 19. Portakal O. Biyolojik ölçümler ve nanopartiküller. Türk Biyokimya Derg, 2008; 33 (1): 35–8.
19. 20. Bainbridge WS. Perceptions of science essay. privacy and property on the net: research questions. Science, 2003; 302: 1686-7.
20. 21. Scholz RW, Siegrist M. Low risks, high public concern? the cases of persistent organic pollutants (POPs), heavy metals, and nanotech particles. IED Working Paper 5, Institute for Environmental Decisions, Zurich, 2008.
21. 22. Lanone S, Boczkowski J. Biomedical applications and potential health risks of nanomaterials: molecular mechanisms. Curr Mol Med, 2006; 6: 651-63.
22. 23. Logothetidis S. Nanotechnology in medicine: the medicine of tomorrow and nanomedicine. Hippokratia, 2006; 10 (1): 7- 21.
23. 24. Gonzalez L, Lison D, Kirsch-Volders M. Genotoxicity of engineered nanomaterials: a critical review. Nanotoxicol, 2008; 2 (4): 252-73.
24. 25. Hoet P, Hohlfeld I, Salata O. Nanoparticles-known and unknown health risks. J Nanobiotechnology, 2004; 2: 1–15.
25. 26. Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases, 2007; 2 (4): 17-71.
26. 27. Shatkin JA, Abbott LC, Bradley AE, Canady RA, Guidotti T, Kulinowski KM, et al. Nano risk analysis: advancing the science for nanomaterials risk management. Risk Anal, 2010; 30 (11): 1680-7.
27. 28. http://www.nano.gov (14.02.2012).
28. 29. Pfuhler S, Elespuru R, Aardema MJ, Doak SH, Donner EM, Honma M, et al. Genotoxicity of nanomaterials: refining strategies and tests for hazard identification. Environ Mol Mutagen, 2013; 54 (4): 229-39.
29. 30. Lacerda L, Bianco A, Prato M, Kostarelos K. Carbon nanotubes as nanomedicines: from toxicology to pharmacology. Adv Drug Deliv Rev, 2006; 58: 1460-70.
30. 31. Donaldson K, Poland CA, Schins RPF. Possible genotoxic mechanisms of nanoparticles: criteria for improved test strategies. Nanotoxicol, 2010; 4 (4): 414-20.
31. 32. Zeiger E. History and rationale of genetic toxicology testing: an impersonal, and sometimes personal, view. Environ Mol Mutagen, 2004; 44: 363-71.
32. 33. Atlı Şekeroğlu Z, Şekeroğlu V. Genetik toksisite testleri. Tübav Bil Derg, 2011; 4 (3): 221-9.
33. 34. Xie H, Mason MM, Wise Sr, JP. Genotoxicity of metal nanoparticles. Rev Environ Health, 2011; 26 (4): 251-68.
34. 35. Mantovani D. Shape memory alloys: properties and biomedical applications. JOM, 2000; 52 (10): 36-44.
35. 36. Niinomi M. Recently metallic materials for biomedical applications. Metall Mater Trans A, 2002; 33 (3): 477-86.
36. 37. Revell PA. The biological effects of nanoparticles. Nanotechnol Percept, 2006; 2: 283–98.
37. 38. Gonzalez L, Sanderson BJS, Kirsch-Volders M. Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials. Mutagenesis, 2011; 26 (1): 185–91.
38. 39. Ishikawa Y, Nakagawa K, Satoh Y, Kitagawa T, Sugano H, Hirano T, et al. Characteristics of chromate workers’ cancers, chromium lung deposition and precancerous bronchial lesions: an autopsy study. Br J Cancer, 1994; 70: 160–6.
39. 40. Doherty AT, Howell RT, Ellis LA, Bisbinas I, Learmonth ID, Newson R, et al. Increased chromosome translocations and aneuploidy in peripheral blood lymphocytes of patients having revision arthroplasty of the hip. J Bone Joint Surg, 2001; 83: 1075-81.
40. 41. Xie H, Wise SS, Holmesa AL, Xud B, Wakemand TP, Pelsue SC, et al. Carcinogenic lead chromate induces DNA double-strand breaks in human lung cells. Mutat Res, 2005; 586: 160–72.
41. 42. Papageorgiou I, Brown C, Schins R, Singh S, Newson R, Davis S, et al. The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. Biomaterials, 2007; 28: 2946–58.
42. 43. Colognato R, Bonelli A, Ponti J, Farina M, Bergamaschi E, Sabbioni E, et al. Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro. Mutagenesis, 2008; 23: 377–82.
43. 44. Ponti J, Sabbioni E, Munaro B, Broggi F, Marmorato P, Franchini F, et al. Genotoxicity and morphological transformation induced by cobalt nanoparticles and cobalt chloride: an in vitro study in Balb/3T3 mouse fibroblasts. Mutagenesis, 2009; 24: 439–45.
44. 45. Parry MC, Bhabra G, Sood A, Machado F, Cartwright L, Saunders M, et al. Thresholds for indirect DNA damage across cellular barriers for orthopaedic biomaterials. Biomaterials, 2010; 31 (16): 4477-83.
45. 46. Tsaousi A, Jones E, Case CP. The in vitro genotoxicity of orthopaedic ceramic (Al2 O3 ) and metal (CoCr alloy) particles. Mutat Res, 2010; 697 (2): 1-9.
46. 47. Signorello LB, Ye W, Fryzek JP, Lipworth L, Fraumeni JF Jr, Blot WJ, et al. Nationwide study of cancer risk among hip replacement patients in Sweden. J Natl Cancer Inst, 2001; 93: 1405-10.
47. 48. Goldacre MJ, Wotton CJ, Seagroatt V, Yeates D. Cancer following hip and knee arthroplasty: record linkage study. Br J Cancer, 2005; 92: 1298-1301.
48. 49. MacDonald SJ. Can a safe level for metal ions in patients with metal-on-metal total hip arthroplasties be determined? J Arthroplasty, 2004; 19 (8): 71-7.
49. 50. Smith AJ, Dieppe P, Porter M, Blom AW. Risk of cancer in first seven years after metal-on-metal hip replacement compared with other bearings and general population: linkage study between the National Joint Registry of England and Wales and hospital episode statistics. BMJ, 2012; 344: 2383.