Genotoxicity of phthalates

Toxicology Mechanisms and Methods

Volumn 24, Issue 9, 2014, Pages 616-626

  Erkekoglu, Pinar ^a   Kocer Gumusel, Belma ^a  

^a HACETTEPE UNIVERSITY   (Turkey)

Author keywords

Comet assay; Di(2 ethylhexyl)phthalate; Genotoxicity; Phthalate; Reactive oxygen species

Indexed keywords

ENDOCRINE DISRUPTOR; ENVIRONMENTAL CHEMICAL; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; PEROXISOME PROLIFERATOR; PHTHALIC ACID; PHTHALIC ACID BENZYL BUTYL ESTER; PHTHALIC ACID BIS(2 ETHYLHEXYL) ESTER; PHTHALIC ACID DIBUTYL ESTER; PHTHALIC ACID DIETHYL ESTER; PHTHALIC ACID DIMETHYL ESTER; PHTHALIC ACID DIOCTYL ESTER; PHTHALIC ACID ESTER; REACTIVE OXYGEN METABOLITE; PHTHALIC ACID DERIVATIVE;

AMES TEST; ARTICLE; CHROMOSOME ABERRATION; COMET ASSAY; GENOTOXICITY; HUMAN; IN VITRO STUDY; INFLAMMATORY DISEASE; LIVER CARCINOGENESIS; MICRONUCLEUS TEST; MUTAGENIC ACTIVITY; NEOPLASM; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; ANIMAL; CHEMICALLY INDUCED; EXPERIMENTAL LIVER NEOPLASM; METABOLISM; MUTAGEN TESTING;

ANIMALS; HUMANS; LIVER NEOPLASMS, EXPERIMENTAL; MUTAGENICITY TESTS; PHTHALIC ACIDS; REACTIVE OXYGEN SPECIES;

EID: 84912122483     PISSN: 15376516     EISSN: 15376524     Source Type: Journal    
DOI: 10.3109/15376516.2014.960987     Document Type: Article

References (99)

1. Ahbab MA, Ündeʇer Ü, Barlas N, Başaran N. (2014). In utero exposure to dicyclohexyl and di-n-hexyl phthalate possess genotoxic effects on testicular cells of male rats after birth in the comet and TUNEL assays. Hum Exp Toxicol 33:230-9
2. Akingbemi BT, Hardy MP. (2001). Oestrogenic and antiandrogenic chemicals in the environment: effects on male reproductive health. Ann Med 33:391-403
3. Anderson D, Dobrzyńska MM, Basaran N. (1997). Effect of various genotoxins and reproductive toxins in human lymphocytes and sperm in the Comet assay. Teratog Carcinog Mutagen 17:29-43
4. Anderson D, Yu TW, Hincal F. (1999). Effect of some phthalate esters in human cells in the Comet assay. Teratog Carcinog Mutagen 19: 275-80
5. Andrade AJ, Grande SW, Talsness CE, et al. (2006). A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats. Toxicology 228:85-97
6. Ashby J, Tennant RW. (1994). Prediction of rodent carcinogenicity for 44 chemicals: results. Mutagenesis 9:7-15
7. Astill B, Barber E, Lington A, et al. (1986). Chemical industry voluntary test program for phthalate esters: health effects studies. Environ Health Perspect 65:329-36
8. Astill BD, Gingell R, Guest D, et al. (1996). Oncogenicity testing of 2-ethylhexanol in Fischer 344 rats and B6C3F1 mice. Fundam Appl Toxicol 31:29-41
9. Azqueta A, Collins AR. (2013). The essential Comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 87: 949-68
10. Bentley P, Calder I, Elcombe C, et al. (1993). Hepatic peroxisome proliferation in rodents and its significance for humans. Food Chem Toxicol 31:857-907
11. Bility MT, Thompson JT, McKee RH, et al. (2004). Activation of mouse and human peroxisome proliferator-Activated receptors (PPARs) by phthalate monoesters. Toxicol Sci 82:170-82
12. Biscardi D, Monarca S, De Fusco R, et al. (2003). Evaluation of the migration of mutagens/carcinogens from PET bottles into mineral water by Tradescantia/micronuclei test, Comet assay on leukocytes and GC/MS. Sci Total Environ 302:101-8
13. Blom A, Ekman E, Johannisson A, et al. (1998). Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7). Arch Environ Contam Toxicol 34:306-10
14. Cattley RC, DeLuca J, Elcombe C, et al. (1998). Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans?. Regul Toxicol Pharmacol 27:47-60
15. Choi S, Park SY, Jeong J, et al. (2010). Identification of toxicological biomarkers of di(2-ethylhexyl) phthalate in proteins secreted by HepG2 cells using proteomic analysis. Proteomics 10: 1831-46
16. Clare G. (2012). The in vitro mammalian chromosome aberration test. Method Mol Biol 817:69-91
17. Collins A, Koppen G, Valdiglesias V, et al. (2014). The Comet assay as a tool for human biomonitoring studies: the ComNet project. Mutat Res Rev Mutat Res 759:27-39
18. Dalgaard M, Ostergaard G, Lam HR, et al. (2000). Toxicity study of di(2-ethylhexyl) phthalate (DEHP) in combination with acetone in rats. Pharmacol Toxicol 86:92-100
19. D'Autréaux B, Toledano MB. (2007). ROS as signaling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813-24
20. Decordier I, Kirsch-Volders M. (2006). The in vitro micronucleus test: from past to future. Mutat Res 607:2-4
21. Doull J, Cattley R, Elcombe C, et al. (1999). A cancer risk assessment of di(2-ethylhexyl) phthalate: application of the new US EPA risk assessment guidelines. Regul Toxicol Pharmacol 29:327-57
22. Durmaz E, Ozmert EN, Erkekoglu P, et al. (2010). Plasma phthalate levels in pubertal gynecomastia. Pediatrics 125:e122-9
23. Duty SM, Singh NP, Silva MJ, et al. (2003). The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral Comet assay. Environ Health Perspect 111: 1164-9
24. Elliott BM, Elcombe CR. (1987). Lack of DNA damage or lipid peroxidation measured in vivo in the rat liver following treatment with peroxisomal proliferators. Carcinogenesis 8:1213-18
25. Erkekoglu P, Rachidi W, De Rosa V, et al. (2010a). Protective effect of selenium supplementation on the genotoxicity of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate treatment in LNCaP cells. Free Radic Biol Med 49:559-66
26. Erkekoglu P, Rachidi W, Yuzugullu OG, et al. (2010b). Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium. Toxicol Appl Pharmacol 248:52-62
27. Erkekoglu P, Rachidi W, YüzügüllüOG, et al. (2011a). Induction of ROS, p53, p21 in DEHP- And MEHP-exposed LNCaP cells-protection by selenium compounds. Food Chem Toxicol 49:1565-71
28. Erkekoglu P, Zeybek ND, Giray B, et al. (2011b). Reproductive toxicity of di(2-ethylhexyl) phthalate in selenium-supplemented and seleniumdeficient rats. Drug Chem Toxicol 34:379-89
29. Erkekoglu P. (2012). Protection studies by antioxidants using single cell gel electrophoresis Comet assay. In: Magdeldin S, ed. Gel electrophoresis - Advanced techniques. Rijeka: InTech, 413-46
30. Erkekoglu P, Zeybek ND, Giray B, et al. (2012a). The effects of di(2-ethylhexyl) phthalate exposure and selenium nutrition on sertoli cell vimentin structure and germ-cell apoptosis in rat testis. Arch Environ Contam Toxicol 62:539-47
31. Erkekoglu P, Giray BK, Kizilgün M, et al. (2012b). Di(2-ethylhexyl) phthalate-induced renal oxidative stress in rats and protective effect of selenium. Toxicol Mech Method 22:415-23
32. Erkekoglu P, Giray BK, Kizilgun M, et al. (2012c). Thyroidal effects of di-(2-ethylhexyl) phthalate in rats of different selenium status. J Environ Pathol Toxicol Oncol 31:143-53
33. Erkekoglu P, Zeybek ND, Giray BK, et al. (2014). The effects of di(2-ethylhexyl) phthalate on rat liver in relation to selenium status. Int J Exp Pathol 95:64-77
34. Fan J, Traore K, Li W, et al. (2010). Molecular mechanisms mediating the effect of mono-(2-ethylhexyl) phthalate on hormone-stimulated steroidogenesis in MA-10 mouse tumor Leydig cells. Endocrinology 151:3348-62
35. Faust F, Kassie F, Knasmüller S, et al. (2004). The use of the alkaline Comet assay with lymphocytes in human biomonitoring studies. Mutat Res 566:209-29
36. Fenech M. (2000). The in vitro micronucleus technique. Mutat Res 455: 81-95
37. Franco R, Schoneveld O, Georgakilas AG, Panayiotidis MI. (2008). Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett 266:6-11
38. Frederiksen H, Jensen TK, Jørgensen N, et al. (2014). Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012. Reproduction 147: 555-65
39. Frederiksen H, Sørensen K, Mouritsen A, et al. (2012). High urinary phthalate concentration associated with delayed pubarche in girls. Int J Androl 35:216-26
40. Gazouli M, Yao ZX, Boujrad N, et al. (2002). Effect of peroxisome proliferators on Leydig cell peripheral-Type benzodiazepine receptor gene expression, hormone-stimulated cholesterol transport and steroidogenesis: role of the peroxisome proliferator-Activator receptor alpha. Endocrinology 143:2571-83
41. Ge RS, Chen GR, Tanrikut C, Hardy MP. (2007). Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod Toxicol 23:366-73
42. Gruber J, Schaffer S, Halliwell B. (2008). The mitochondrial free radical theory of ageing-where do we stand?. Front Biosci 13:6554-79
43. Gutzkow KB, Langleite TM, Meier S, et al. (2013). High-Throughput Comet assay using 96 minigels. Mutagenesis 28:333-40
44. Halliwell B, Cross CE. (1994). Oxygen-derived species: their relation to human Disease and environmental stress. Environ Health Perspect 102:5-12
45. Halliwell B. (2012). Free radicals and antioxidants: updating a personal view. Nutr Rev 70:257-65
46. Hauser R, Meeker JD, Singh NP, et al. (2007). DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod 22:688-95
47. Heaton PR, Reed CF, Mann SJ, et al. (2002). Role of dietary antioxidants to protect against DNA damage in adult dogs. J Nutr 132:1720S-4S
48. Heudorf U, Mersch-Sundermann V, Angerer J. (2007). Phthalates: toxicology and exposure. Int J Hyg Environ Health 210:623-34
49. Huber WW, Grasl-Kraupp B, Schulte-Hermann R. (1996). Hepatocarcinogenic potential of di(2-ethylhexyl)phthalate in rodents and its implications on human risk. Crit Rev Toxicol 26: 365-481
50. Ishihara M, Itoh M, Miyamoto K, et al. (2000). Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat. Int J Androl 23:85-94
51. Johnson GE. (2012). Mammalian cell HPRT gene mutation assay: test methods. Method Mol Biol 817:55-67
52. Jones HB, Garside DA, Liu R, Roberts JC. (1993). The influence of phthalate esters on Leydig cell structure and function in vitro and in vivo. Exp Mol Pathol 58:179-93
53. Just AC, Whyatt RM, Miller RL, et al. (2012). Children's urinary phthalate metabolites and fractional exhaled nitric oxide in an urban cohort. Am J Respir Crit Care Med 186:830-7
54. Kaufmann W, Deckardt K, McKee RH, et al. (2002). Tumor induction in mouse liver: di-isononyl phthalate acts via peroxisome proliferation. Regul Toxicol Pharmacol 36:175-83
55. Kim MY, Kim YC, Cho MH. (2002). Combined treatment with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and dibutyl phthalate enhances ozone-induced genotoxicity in B6C3F1 mice. Mutagenesis 17:331-6
56. Klaunig JE, Babich MA, Baetcke KP, et al. (2003). PPARalpha agonistinduced rodent tumors: modes of action and human relevance. Crit Rev Toxicol 33:655-780
57. Kleinsasser NH, Kastenbauer ER, Weissacher H, et al. (2000). Phthalates demonstrate genotoxicity on human mucosa of the upper aerodigestive tract. Environ Mol Mutagen 35:9-12
58. Kleinsasser NH, Wallner BC, Kastenbauer ER, et al. (2001). Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human lymphocytes and mucosal cells. Teratog Carcinog Mutagen 21:189-96
59. Kluwe WM, Huff JE, Matthews HB, et al. (1985). Comparative chronic toxicities and carcinogenic potentials of 2-ethylhexyl-containing compounds in rats and mice. Carcinogenesis 6:1577-83
60. Labow RS, Tocchi M, Rock G. (1986). Contamination of platelet storage bags by phthalate esters. J Toxicol Environ Health 19:591-8
61. Lee KH, Lee BM. (2007). Study of mutagenicities of phthalic acid and terephthalic acid using in vitro and in vivo genotoxicity tests. J Toxicol Environ Health A 70:1329-35
62. Lindahl-Kiessling K, Karlberg I, Olofsson AM. (1989). Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen. Mutat Res 211:77-87
63. McKee RH, Przygoda RT, Chirdon MA, et al. (2000). Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic. J Appl Toxicol 20:491-7
64. Meek M, Chan P. (1994). Bis(2-ethylhexyl)phthalate: evaluation of risks to health from environmental exposure in Canada. J Environ Sci Health Part C 12:179-94
65. Melnick RL. (2001). Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)?. Environ Health Perspect 109:437-42
66. Mettang T, Alscher DM, Pauli-Magnus C, et al. (1999). Phthalic acid is the main metabolite of the plasticizer di(2-ethylhexyl)phthalate in peritoneal dialysis patients. Adv Perit Dial 15:229-33
67. Mortelmans K, Zeiger E. (2000). The Ames Salmonella/microsome mutagenicity assay. Mutat Res 455:29-60
68. Müller-Tegethoff K, Kasper P, Müller L. (1995). Evaluation studies on the in vitro rat hepatocyte micronucleus assay. Mutat Res 335: 293-307
69. Nakai M, Tabira Y, Asai D, et al. (1999). Binding characteristics of dialkyl phthalates for the estrogen receptor. Biochem Biophys Res Commun 254:311-14
70. Nässberger L, Arbin A, Ostelius J. (1987). Exposure of patients to phthalates from polyvinyl chloride tubes and bags during dialysis. Nephron 45:286-90
71. Nose K. (2000). Role of reactive oxygen species in the regulation of physiological functions. Biol Pharm Bull 23:897-903
72. Novotna B, Topinka J, Solansky I, et al. (2007). Impact of air pollution and genotype variability on DNA damage in Prague policemen. Toxicol Lett 172:37-47
73. O'Brien ML, Spear BT, Glauert HP. (2005). Role of oxidative stress in peroxisome proliferator-mediated carcinogenesis. Crit Rev Toxicol 35:61-88
74. Painter RB, Cleaver JE. (1969). Repair replication, unscheduled DNA synthesis, and the repair of mammalian DNA. Radiat Res 37: 451-66
75. Park SY, Choi J. (2007). Cytotoxicity, genotoxicity and ecotoxicity assay using human cell and environmental species for the screening of the risk from pollutant exposure. Environ Int 33:817-22
76. Phillips BJ, James TE, Gangolli SD. (1982). Genotoxicity studies of di(2-ethylhexyl)phthalate and its metabolites in CHO cells. Mutat Res 102:297-304
77. Phillips BJ, Anderson D, Gangolli SD. (1986). Studies on the genetic effects of phthalic acid esters on cells in culture. Environ Health Perspect 65:263-6
78. Reddy JK, Rao MS. (1989). Oxidative DNA damage caused by persistent peroxisome proliferation: its role in hepatocarcinogenesis. Mutat Res 214:63-8
79. Richburg JH, Boekelheide K. (1996). Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes. Toxicol Appl Pharmacol 137: 42-50
80. Rusyn I, Rose ML, Bojes HK, Thurman RG. (2000a). Novel role of oxidants in the molecular mechanism of action of peroxisome proliferators. Antioxid Redox Signal 2:607-21
81. Rusyn I, Denissenko MF, Wong VA, et al. (2000b). Expression of base excision repair enzymes in rat and mouse liver is induced by peroxisome proliferators and is dependent upon carcinogenic potency. Carcinogenesis 21:2141-5
82. Rusyn I, Peters JM, Cunningham ML. (2006). Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit Rev Toxicol 36:459-79
83. Saeidnia S, Abdollahi M. (2013). Toxicological and pharmacological concerns on oxidative stress and related diseases. Toxicol Appl Pharmacol 273:442-55
84. Seo KW, Kim KB, Kim YJ, et al. (2004). Comparison of oxidative stress and changes of xenobiotic metabolizing enzymes induced by phthalates in rats. Food Chem Toxicol 42:107-14
85. Shintani H. (1985). Determination of phthalic acid, mono-(2-ethylhexyl) phthalate and di-(2-ethylhexyl) phthalate in human plasma and in blood products. J Chromatogr 337:279-90
86. Silva MJ, Samandar E, Preau Jr JL, et al. (2006). Urinary oxidative metabolites of di(2-ethylhexyl) phthalate in humans. Toxicology 219: 22-32
87. Sjöberg P. Bondesson U. 1985). Determination of di(2-ethylhexyl) phthalate and four of its metabolites in blood plasma by gas chromatography-mass spectrometry. J Chromatogr 344 167-75
88. Smith-Oliver T, Butterworth BE. (1987). Correlation of the carcinogenic potential of di(2-ethylhexyl)phthalate (DEHP) with induced hyperplasia rather than with genotoxic activity. Mutat Res 188:21-8
89. Stenchever MA, Allen MA, Jerominski L, Petersen RV. (1976). Effects of bis(2-ethylhexyl) phthalate on chromosomes of human leukocytes and human fetal lung cells. J Pharm Sci 65:1648-51
90. Tay TW, Andriana BB, Ishii M, et al. (2007). Disappearance of vimentin in Sertoli cells: a mono(2-ethylhexyl) phthalate effect. Int J Toxicol 26:289-95
91. Teitelbaum SL, Mervish N, Moshier EL, et al. (2012). Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environ Res 112:186-93
92. Tinwell H, Ashby J. (1994). Comparative activity of human carcinogens and NTP rodent carcinogens in the mouse bone marrow micronucleus assay: an integrative approach to genetic toxicity data assessment. Environ Health Perspect 102:758-62
93. Turner JH, Petricciani JC, Crouch ML, Wenger S. (1974). An evaluation of the effects of diethylhexyl phthalate (DEHP) on mitotically capable cells in blood packs. Transfusion 14:560-6
94. Veal EA, Day AM, Morgan BA. (2007). Hydrogen peroxide sensing and signaling. Mol Cell 26:1-14
95. Waring RH, Harris RM. (2005). Endocrine disrupters: a human risk?. Mol Cell Endocrinol 244:2-9
96. Willhite CC. (2001). Weight-of-evidence versus strength-of-evidence in toxicologic hazard identification: di(2-ethylhexyl)phthalate (DEHP). Toxicology 160:219-26
97. Wormuth M, Scheringer M, Vollenweider M, et al. (2006). What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?. Risk Anal 26:803-24
98. Yeldani AV, Milano M, Subbarao V, et al. (1989). Evaluation of liver cell proliferation During ciprofibrate-induced hepatocarcinogenesis. Cancer Lett 47:21-7
99. Zacharewski TR, Meek MD, Clemons JH, et al. (1998). Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters. Toxicol Sci 46:282-93