BibTex RIS Kaynak Göster

Apoptotic Cell Death and Its Importance in Toxicological Response

Yıl 2017, Cilt: 6 Sayı: 2, 499 - 504, 01.06.2017

Öz

Backround/Aim: In multicellular organisms, it is necessary to be maintained adequate number of cells in tissues and organs to prevent diseases. The role of apoptosis, which is one of the cell death types, in the sustaining delicate balance in all mammalian tissues is important. Apoptosis is known to be a vital component of various processes such as normal cell cycle, appropriate development and functioning of the immune system, hormone dependent atrophy, embryonic development and chemically induced cell death. Acute and chronic toxicity that are occured by a variety of xenobiotic chemicals, radiation and toxins, can cause neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, which depend on apoptotic processes. In this review, the role of apoptotic cell death was evaluated in terms of toxicological responses caused by a variety of environmental pollutants and chemicals. Conclusion: Cell death and cell death mechanisms are one of the most important elements to focus in toxicological assessment.

Kaynakça

  • Ahamed M, Akhtar MJ, Raja M, Ahmad I, Siddiqui MKJ, Alsalhi MS, Alrokayan SA (2011). ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress. Nanomedicine: Nanotechnology, Biology and Medicine, 7(6), 904-913.
  • Andersen JL, Kornbluth S (2013). The tangled circuitry of metabolism and apoptosis. Molecular cell, 49(3), 399-410.
  • Andersen JL, Rathmell JC (2015). Cell Death Pathways in Toxicological Response. Mammalian Toxicology, 75-83.
  • Brama M, Politi L, Santini P, Migliaccio S, Scandurra R (2012). Cadmium- induced apoptosis and necrosis in human osteoblasts: role of caspases and mitogen-activated protein kinases pathways. Journal of endocrinological investigation, 35(2), 198-208.
  • Cadenas E, Davies KJ (2000). Mitochondrial free radical generation, oxidative stress, and aging. Free Radical Biology and Medicine, 29(3), 222-230.
  • Carafoli E (2002). Calcium signaling: a tale for all seasons. Proceedings of the National Academy of Sciences, 99(3), 1115-1122.
  • Chen L, Xu B, Liu L, Luo Y, Zhou H, Chen W, Shen T, Han X, Kontos CD, Huang S (2011). Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radical Biology and Medicine, 50(5), 624-632.
  • Corcoran GB, Fix L, Jones DP, Moslen MT, Nicotera P, Oberhammer FA, Buttyan R (1994). Apoptosis: molecular control point in toxicity. Toxicology and applied pharmacology, 128(2), 169-181.
  • Curtin JF, Cotter TG (2003). Live and let die: regulatory mechanisms in Fas-mediated apoptosis. Cellular signalling, 15(11), 983-992.
  • Danial NN, Korsmeyer SJ (2004). Cell death: critical control points. Cell, 116(2), 205-219.
  • Das S, Unni B, Bhattacharjee M, Wann SB, Rao PG (2012). Toxicological effects of arsenic exposure in a freshwater teleost fish, Channa punctatus. African Journal of Biotechnology, 11(19), 4447-4454.
  • Du X, Youle RJ, Fitzgerald DJ, Pastan I (2010). Pseudomonas exotoxin A-mediated apoptosis is Bak dependent and preceded by the degradation of Mcl-1. Molecular and cellular biology, 30(14), 3444- 3452.
  • Elliott MR, Ravichandran KS (2010). Clearance of apoptotic cells: implications in health and disease. The Journal of cell biology, 189(7), 1059-1070.
  • Elmore S (2007). Apoptosis: a review of programmed cell death. Toxicologic pathology, 35(4), 495-516.
  • Gennari A, Viviani B, Galli CL, Marinovich M, Pieters R, Corsini E (2000). Organotins induce apoptosis by disturbance of [Ca2+] i and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. Toxicology and applied pharmacology, 169(2), 185-190.
  • Guvenc D, Aksoy A, Gacar A, Atmaca E, Das KY, Guvenc T (2014). Evaluation of changes in monoamine levels and apoptosis induced by cyfluthrin in rats. Toxicology Research, 3(5), 331-340.
  • Guvenc D, Kabak Y, Atmaca E, Aksoy A, Guvenc T (2013a). Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin. Biotechnic & Histochemistry, 88(2), 76-85.
  • Guvenc D, Kabak YB, Atmaca E, Aksoy A, Guvenc T (2013b). Biological significance of the overexpression of HSP70 and alpha B-crystallin in rat substantia nigra exposed to different doses of permethrin. Archives of Industrial Hygiene and Toxicology, 64(1), 47-55.
  • Hasan M, Ahmed M, Akhand A, Ahsan N, Islam M (2010). Toxicological Effects and Molecular Changes Due to Mercury Toxicity in Freshwater Snakehead (Channa punctatus Bloch, 1973). Int. J. Environ. Res, 4(1), 91-98.
  • Hengartner MO (2000). The biochemistry of apoptosis. Nature, 407(6805), 770.
  • Horvitz HR (2003). Nobel lecture: Worms, life and death. Bioscience reports, 23(5), 239-303.
  • Huang C-C, Aronstam RS, Chen D-R, Huang Y-W (2010). Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. Toxicology in vitro, 24(1), 45-55.
  • Kerr JF, Wyllie AH, Currie AR (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer, 26(4), 239.
  • Kroemer G, Galluzzi L, Brenner C (2007). Mitochondrial membrane permeabilization in cell death. Physiological reviews, 87(1), 99-163.
  • Ledda-Columbano G, Coni P, Curto M, Giacomini L, Faa G, Oliverio S, Piacentini M, Columbano A (1991). Induction of two different modes of cell death, apoptosis and necrosis, in rat liver after a single dose of thioacetamide. The American journal of pathology, 139(5), 1099.
  • Ledda-Columbano G, Coni P, Faa G, Manenti G, Columbano A (1992). Rapid induction of apoptosis in rat liver by cycloheximide. The American journal of pathology, 140(3), 545.
  • Lee M-S, Cherla RP, Leyva-Illades D, Tesh VL (2009). Bcl-2 regulates the onset of Shiga toxin 1-induced apoptosis in THP-1 cells. Infection and immunity, 77(12), 5233-5244.
  • Lopez E, Figueroa S, Oset-Gasque M, Gonzalez M (2003). Apoptosis and necrosis: two distinct events induced by cadmium in cortical neurons in culture. British journal of pharmacology, 138(5), 901- 911.
  • Luzio A, Monteiro SM, Fontaínhas-Fernandes AA, Pinto-Carnide O, Matos M, Coimbra AM (2013). Copper induced upregulation of apoptosis related genes in zebrafish (Danio rerio) gill. Aquatic toxicology, 128, 183-189.
  • Mcconkey DJ, Hartzell P, Duddy SK, Hakansson H, Orrenius S (1988). 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science, 242(4876), 256.
  • Nicholson D (1999). Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell death and differentiation, 6(11), 1028-1042.
  • Oh S-H, Lim S-C (2006). A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicology and applied pharmacology, 212(3), 212-223.
  • Omar WA, Zaghloul KH, Abdel-Khalek AA, Abo-Hegab S (2012). Genotoxic effects of metal pollution in two fish species, Oreochromis niloticus and Mugil cephalus, from highly degraded aquatic habitats. Mutation Research/Genetic Toxicology And Environmental Mutagenesis, 746(1), 7-14.
  • Orrenius S (2004). Mitochondrial regulation of apoptotic cell death. Toxicology letters, 149(1), 19-23.
  • Orrenius S, Gogvadze V, Zhivotovsky B (2015). Calcium and mitochondria in the regulation of cell death. Biochemical and Biophysical Research Communications, 460(1), 72-81.
  • Orrenius S, Nicotera P, Zhivotovsky B (2010). Cell death mechanisms and their implications in toxicology. Toxicological Sciences, 119(1), 3-19.
  • Orrenius S, Zhivotovsky B (2006). The Future of Toxicology Does It Matter How Cells Die? Chemical research in toxicology, 19(6), 729- 733.
  • Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2002). Cytochrome c release from mitochondria proceeds by a two-step process. Proceedings of the National Academy of Sciences, 99(3), 1259-1263.
  • Raff MC (1992). Social controls on cell survival and cell death. Nature, 356(6368), 397.
  • Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA, Thompson CB (2000). In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Molecular cell, 6(3), 683-692.
  • Richburg JH (2000). The relevance of spontaneous-and chemically- induced alterations in testicular germ cell apoptosis to toxicology. Toxicology letters, 112, 79-86.
  • Riedl SJ, Salvesen GS (2007). The apoptosome: signalling platform of cell death. Nature reviews. Molecular cell biology, 8(5), 405.
  • Roberts RA, Nebert DW, Hickman JA, Richburg JH, Goldsworthy TL (1997). Perturbation of the mitosis/apoptosis balance: a fundamental mechanism in toxicology. Toxicological Sciences, 38(2), 107-115.
  • Roy S, Nicholson DW (2000). Cross-talk in cell death signaling. Journal of Experimental Medicine, 192(8), F21-F26.
  • Sun X-M, Carthew P, Dinsdale D, Snowden RT, Cohen GM (1994). The involvement of apoptosis in etoposide-induced thymic atrophy. Toxicology and applied pharmacology, 128(1), 78-85.
  • Vandebriel RJ, De Jong WH (2012). A review of mammalian toxicity of ZnO nanoparticles. Nanotechnology, science and applications, 5, 61.
  • Wang B, Feng L, Jiang W-D, Wu P, Kuang S-Y, Jiang J, Tang L, Tang W-N, Zhang Y-A, Liu Y (2015). Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF- κB, TOR and Nrf2 signaling molecules in the gills of fish: preventive role of arginine. Aquatic toxicology, 158, 125-137.
  • Wyllie A. (1987). Apoptosis: cell death under homeostatic control Mechanisms and Models in Toxicology (pp. 3-10): Springer.
  • Youle RJ, Strasser A (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nature reviews. Molecular cell biology, 9(1), 47.
  • Yuan J, Horvitz HR (1990). The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Developmental biology, 138(1), 33-41.
  • Zheng G-H, Liu C-M, Sun J-M, Feng Z-J, Cheng C (2014). Nickel-induced oxidative stress and apoptosis in Carassius auratus liver by JNK pathway. Aquatic toxicology, 147, 105-111.
  • Zhou Z, Wang C, Liu H, Huang Q, Wang M, Lei Y (2013). Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. International journal of medical sciences, 10(11), 1485.

Apoptotik Hücre Ölümü ve Toksikolojik Yanıtta Önemi

Yıl 2017, Cilt: 6 Sayı: 2, 499 - 504, 01.06.2017

Öz

Özbilgi/Amaç: Çok hücreli organizmalarda hastalıkların önlenmesi için doku ve organlarda uygun hücre sayısının devam ettirilmesi zorunludur. Hücre sayısındaki denge yeni hücre oluşumu ve sabit bir ölüm hızıyla sağlanır. Tüm memeli dokularında bu hassas dengenin devam ettirilmesinde hücre ölüm tiplerinden biri olan apoptozun rolü büyüktür. Apoptoz, normal hücre döngüsü, bağışıklık sisteminin düzgün gelişimi ve işleyişi, hormona bağımlı atrofi, embriyonik gelişme ve kimyasal kaynaklı hücre ölümü gibi çeşitli işlemlerin hayati bir bileşeni olarak kabul edilir. Çeşitli ksenobiyotik kimyasallar, radyasyon ve toksinlerin neden olduğu akut ve kronik toksisite sonucu oluşan apoptotik sürece bağlı olarak nörodejeneratif hastalıklar, iskemik hasar, otoimmün bozukluklar ve birçok kanser türü meydana gelebilmektedir. Bu derlemede apoptotik hücre ölümünün özellikle çeşitli çevresel kirleticiler ve kimyasalların neden olduğu toksikolojik yanıt açısından rolü değerlendirilmiştir. Sonuç: Hücre ölümü ve hücre ölüm mekanizmaları toksikolojik değerlendirmelerde odaklanılması gereken önemli unsurlardan biridir.

Kaynakça

  • Ahamed M, Akhtar MJ, Raja M, Ahmad I, Siddiqui MKJ, Alsalhi MS, Alrokayan SA (2011). ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress. Nanomedicine: Nanotechnology, Biology and Medicine, 7(6), 904-913.
  • Andersen JL, Kornbluth S (2013). The tangled circuitry of metabolism and apoptosis. Molecular cell, 49(3), 399-410.
  • Andersen JL, Rathmell JC (2015). Cell Death Pathways in Toxicological Response. Mammalian Toxicology, 75-83.
  • Brama M, Politi L, Santini P, Migliaccio S, Scandurra R (2012). Cadmium- induced apoptosis and necrosis in human osteoblasts: role of caspases and mitogen-activated protein kinases pathways. Journal of endocrinological investigation, 35(2), 198-208.
  • Cadenas E, Davies KJ (2000). Mitochondrial free radical generation, oxidative stress, and aging. Free Radical Biology and Medicine, 29(3), 222-230.
  • Carafoli E (2002). Calcium signaling: a tale for all seasons. Proceedings of the National Academy of Sciences, 99(3), 1115-1122.
  • Chen L, Xu B, Liu L, Luo Y, Zhou H, Chen W, Shen T, Han X, Kontos CD, Huang S (2011). Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radical Biology and Medicine, 50(5), 624-632.
  • Corcoran GB, Fix L, Jones DP, Moslen MT, Nicotera P, Oberhammer FA, Buttyan R (1994). Apoptosis: molecular control point in toxicity. Toxicology and applied pharmacology, 128(2), 169-181.
  • Curtin JF, Cotter TG (2003). Live and let die: regulatory mechanisms in Fas-mediated apoptosis. Cellular signalling, 15(11), 983-992.
  • Danial NN, Korsmeyer SJ (2004). Cell death: critical control points. Cell, 116(2), 205-219.
  • Das S, Unni B, Bhattacharjee M, Wann SB, Rao PG (2012). Toxicological effects of arsenic exposure in a freshwater teleost fish, Channa punctatus. African Journal of Biotechnology, 11(19), 4447-4454.
  • Du X, Youle RJ, Fitzgerald DJ, Pastan I (2010). Pseudomonas exotoxin A-mediated apoptosis is Bak dependent and preceded by the degradation of Mcl-1. Molecular and cellular biology, 30(14), 3444- 3452.
  • Elliott MR, Ravichandran KS (2010). Clearance of apoptotic cells: implications in health and disease. The Journal of cell biology, 189(7), 1059-1070.
  • Elmore S (2007). Apoptosis: a review of programmed cell death. Toxicologic pathology, 35(4), 495-516.
  • Gennari A, Viviani B, Galli CL, Marinovich M, Pieters R, Corsini E (2000). Organotins induce apoptosis by disturbance of [Ca2+] i and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. Toxicology and applied pharmacology, 169(2), 185-190.
  • Guvenc D, Aksoy A, Gacar A, Atmaca E, Das KY, Guvenc T (2014). Evaluation of changes in monoamine levels and apoptosis induced by cyfluthrin in rats. Toxicology Research, 3(5), 331-340.
  • Guvenc D, Kabak Y, Atmaca E, Aksoy A, Guvenc T (2013a). Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin. Biotechnic & Histochemistry, 88(2), 76-85.
  • Guvenc D, Kabak YB, Atmaca E, Aksoy A, Guvenc T (2013b). Biological significance of the overexpression of HSP70 and alpha B-crystallin in rat substantia nigra exposed to different doses of permethrin. Archives of Industrial Hygiene and Toxicology, 64(1), 47-55.
  • Hasan M, Ahmed M, Akhand A, Ahsan N, Islam M (2010). Toxicological Effects and Molecular Changes Due to Mercury Toxicity in Freshwater Snakehead (Channa punctatus Bloch, 1973). Int. J. Environ. Res, 4(1), 91-98.
  • Hengartner MO (2000). The biochemistry of apoptosis. Nature, 407(6805), 770.
  • Horvitz HR (2003). Nobel lecture: Worms, life and death. Bioscience reports, 23(5), 239-303.
  • Huang C-C, Aronstam RS, Chen D-R, Huang Y-W (2010). Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. Toxicology in vitro, 24(1), 45-55.
  • Kerr JF, Wyllie AH, Currie AR (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer, 26(4), 239.
  • Kroemer G, Galluzzi L, Brenner C (2007). Mitochondrial membrane permeabilization in cell death. Physiological reviews, 87(1), 99-163.
  • Ledda-Columbano G, Coni P, Curto M, Giacomini L, Faa G, Oliverio S, Piacentini M, Columbano A (1991). Induction of two different modes of cell death, apoptosis and necrosis, in rat liver after a single dose of thioacetamide. The American journal of pathology, 139(5), 1099.
  • Ledda-Columbano G, Coni P, Faa G, Manenti G, Columbano A (1992). Rapid induction of apoptosis in rat liver by cycloheximide. The American journal of pathology, 140(3), 545.
  • Lee M-S, Cherla RP, Leyva-Illades D, Tesh VL (2009). Bcl-2 regulates the onset of Shiga toxin 1-induced apoptosis in THP-1 cells. Infection and immunity, 77(12), 5233-5244.
  • Lopez E, Figueroa S, Oset-Gasque M, Gonzalez M (2003). Apoptosis and necrosis: two distinct events induced by cadmium in cortical neurons in culture. British journal of pharmacology, 138(5), 901- 911.
  • Luzio A, Monteiro SM, Fontaínhas-Fernandes AA, Pinto-Carnide O, Matos M, Coimbra AM (2013). Copper induced upregulation of apoptosis related genes in zebrafish (Danio rerio) gill. Aquatic toxicology, 128, 183-189.
  • Mcconkey DJ, Hartzell P, Duddy SK, Hakansson H, Orrenius S (1988). 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science, 242(4876), 256.
  • Nicholson D (1999). Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell death and differentiation, 6(11), 1028-1042.
  • Oh S-H, Lim S-C (2006). A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicology and applied pharmacology, 212(3), 212-223.
  • Omar WA, Zaghloul KH, Abdel-Khalek AA, Abo-Hegab S (2012). Genotoxic effects of metal pollution in two fish species, Oreochromis niloticus and Mugil cephalus, from highly degraded aquatic habitats. Mutation Research/Genetic Toxicology And Environmental Mutagenesis, 746(1), 7-14.
  • Orrenius S (2004). Mitochondrial regulation of apoptotic cell death. Toxicology letters, 149(1), 19-23.
  • Orrenius S, Gogvadze V, Zhivotovsky B (2015). Calcium and mitochondria in the regulation of cell death. Biochemical and Biophysical Research Communications, 460(1), 72-81.
  • Orrenius S, Nicotera P, Zhivotovsky B (2010). Cell death mechanisms and their implications in toxicology. Toxicological Sciences, 119(1), 3-19.
  • Orrenius S, Zhivotovsky B (2006). The Future of Toxicology Does It Matter How Cells Die? Chemical research in toxicology, 19(6), 729- 733.
  • Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2002). Cytochrome c release from mitochondria proceeds by a two-step process. Proceedings of the National Academy of Sciences, 99(3), 1259-1263.
  • Raff MC (1992). Social controls on cell survival and cell death. Nature, 356(6368), 397.
  • Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA, Thompson CB (2000). In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Molecular cell, 6(3), 683-692.
  • Richburg JH (2000). The relevance of spontaneous-and chemically- induced alterations in testicular germ cell apoptosis to toxicology. Toxicology letters, 112, 79-86.
  • Riedl SJ, Salvesen GS (2007). The apoptosome: signalling platform of cell death. Nature reviews. Molecular cell biology, 8(5), 405.
  • Roberts RA, Nebert DW, Hickman JA, Richburg JH, Goldsworthy TL (1997). Perturbation of the mitosis/apoptosis balance: a fundamental mechanism in toxicology. Toxicological Sciences, 38(2), 107-115.
  • Roy S, Nicholson DW (2000). Cross-talk in cell death signaling. Journal of Experimental Medicine, 192(8), F21-F26.
  • Sun X-M, Carthew P, Dinsdale D, Snowden RT, Cohen GM (1994). The involvement of apoptosis in etoposide-induced thymic atrophy. Toxicology and applied pharmacology, 128(1), 78-85.
  • Vandebriel RJ, De Jong WH (2012). A review of mammalian toxicity of ZnO nanoparticles. Nanotechnology, science and applications, 5, 61.
  • Wang B, Feng L, Jiang W-D, Wu P, Kuang S-Y, Jiang J, Tang L, Tang W-N, Zhang Y-A, Liu Y (2015). Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF- κB, TOR and Nrf2 signaling molecules in the gills of fish: preventive role of arginine. Aquatic toxicology, 158, 125-137.
  • Wyllie A. (1987). Apoptosis: cell death under homeostatic control Mechanisms and Models in Toxicology (pp. 3-10): Springer.
  • Youle RJ, Strasser A (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nature reviews. Molecular cell biology, 9(1), 47.
  • Yuan J, Horvitz HR (1990). The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Developmental biology, 138(1), 33-41.
  • Zheng G-H, Liu C-M, Sun J-M, Feng Z-J, Cheng C (2014). Nickel-induced oxidative stress and apoptosis in Carassius auratus liver by JNK pathway. Aquatic toxicology, 147, 105-111.
  • Zhou Z, Wang C, Liu H, Huang Q, Wang M, Lei Y (2013). Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. International journal of medical sciences, 10(11), 1485.
Toplam 52 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Research Article
Yazarlar

Dilek Güvenç Bu kişi benim

Tolga Güvenç Bu kişi benim

Yayımlanma Tarihi 1 Haziran 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 6 Sayı: 2

Kaynak Göster

APA Güvenç, D., & Güvenç, T. (2017). Apoptotik Hücre Ölümü ve Toksikolojik Yanıtta Önemi. Animal Health Production and Hygiene, 6(2), 499-504.