Arzu YAVUZ, Mehmet TOPAKTAŞ, - *, Erman Salih İSTİFLİ

In Vitro Genotoxic Effects of Benzoyl Peroxide in Human Peripheral Lymphocytes

The aim of the present research was to investigate the genotoxic potency of benzoyl peroxide (BPO), a whitener of flour and cheese, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests in human peripheral lymphocytes. Cells were exposed to 25, 50, 75, and 100 µg/mL concentrations of BPO for 24 and 48 h. BPO induced SCEs only at the highest concentration (100 µg/mL) for 48 h treatment. Furthermore, BPO induced CAs at 75 and 100 µg/mL concentrations for 24 h treatment, and at all concentrations for 48 h treatment. BPO induced CAs in a dose-dependent manner for 24 and 48 h treatment periods. Increased level of MN formation induced by BPO was only observed for the 48 h treatment period at the 2 highest concentrations (75 and 100 µg/mL). Statistically significant reductions in the proliferation index (PI) and mitotic index (MI) were only detected in cultures for the 48-h treatment period.

Anahtar Kelimeler:

Key words: Benzoyl peroxide, human lymphocytes, sister chromatid exchange, chromosome aberration, micronucleus

In Vitro Genotoxic Effects of Benzoyl Peroxide in Human Peripheral Lymphocytes

Keywords:

Key words: Benzoyl peroxide, human lymphocytes, sister chromatid exchange, chromosome aberration, micronucleus,

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1. Binder RL, Aardema MJ, Thompson ED. Benzoyl peroxide: review of experimental carcinogenesis and human safety data. Prog Clin Biol Res 391: 245-94, 1995.
2. Ishidate M. JR, Sofuni T, Yoshikawa K et al. Primary mutagenicity screening of food additives currently used in Japan. Food Chem Toxicol 22: 623-36, 1984.
3. SIDnitial assessment report for SIAM 15; 22-25 October 2002, Boston, USA. (www.inchem.org/documents/sids/sids/ BENZOYLPER.pdf)
4. Dillon D, Combes R, Zeiger E. The effectiveness of Salmonella strains TA100, TA102 and TA104 for detecting mutagenicity of some aldehydes and peroxides. Mutagenesis 13: 19-26, 1998.
5. Epstein SS, Arnold E, Andrea J et al. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol Appl Pharmacol 23: 288-325, 1972.
6. Speit G, Haupter S. On the mechanism of differential giemsa staining of bromodeoxyuridine substituted chromosomes. II. Differences between the demonstration of sister chromatid differentiation replication patterns. Hum Genet 70: 126-129, 1985.
7. Mitelman F, editor. ISCN: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S. Karger; 1995.
8. Paz-y-Miño C, Bustamante G, Sanchez ME et al. Cytogenetic monitoring in a population occupationally exposed to pesticides in Ecuador. Environ Health Perspect 110: 1077-1080, 2002.
9. Mace ML Jr, Daskal Y, Wray W. Scanning electron microscopy of chromosome aberrations. Mutat Res 52: 199-206, 1978.
10. Rothfuss A, Schutz P, Bochum S et al. Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families. Cancer Res 60: 390-394, 2000.
11. Titenko-Holland N, Windham G, Kolachana P et al. Genotoxicity of malathion in human lymphocytes assessed using the micronucleus assay in vitro and in vivo: a study of malathion-exposed workers. Mutat Res 388: 85-95, 1997.
12. Fenech M, Morley AA. Measurement of micronuclei in lymphocytes. Mutat Res 147: 29-36, 1985.
13. Kaya FF, Topaktaş M. Genotoxic effects of potassium bromate on human peripheral lymphocytes in vitro. Mutat Res 626: 48- 52, 2007.
14. Tsuda H, Kushi A, Yoshida D et al. Chromosomal aberrations and sister-chromatid exchanges induced by gaseous nitrogen dioxide in cultured Chinese hamster cells. Mutat Res 89: 303-9, 1981.
15. Yadav JS, Seth N. Effect of NOx on the somatic chromosomes of goldsmiths. Environ Health Perspect 106: 643-7, 1998.
16. Fujie K, Shimazu H, Matsuda M et al. Acute cytogenetic effects of potassium bromate on rat bone marrow cells in vivo. Mutat Res 206: 455-8, 1988.
17. Speit G, Haupter S, Schutz P et al. Comparative evaluation of the genotoxic properties of potassium bromate and potassium superoxide in V79 Chinese hamster cells. Mutat Res 439: 213- 21, 1999.
18. Gensler HL, Bowden GT. Evidence suggesting a dissociation of DNA strand scissions and late-stage promotion of tumor cell phenotype. Carcinogenesis 4: 1507-11, 1983.
19. Saladino AJ, Willey JC, Lechner JF et al. Effects of formaldehyde, acetaldehyde, benzoyl peroxide and hydrogen peroxide on cultured normal human bronchial epithelial cells. Cancer Res 45: 2522-6, 1985.
20. Birnboim HC. DNA strand breaks in human leukocytes induced by superoxide anion, hydrogen peroxide and tumor promoters are repaired slowly compared to breaks induced by ionizing radiation. Carcinogenesis 7: 1511-7, 1986.
21. Hartley JA, Gibson NW, Zwelling LA et al. Association of DNA strand breaks with accelerated terminal differentiation in mouse epidermal cells exposed to tumor promoters. Cancer Res 45: 4867-70, 1985.
22. Hartley JA, Gibson NW, Kilkenny A et al. Mouse keratinocytes derived from initiated skin or papillomas are resistant to DNA strand breakage by benzoyl peroxide: A possible mechanism for tumor promotion mediated by benzoyl peroxide. Carcinogenesis 8: 1827-30, 1987.
23. Swauger JE, Dolan PM, Zweier JL et al. Role of the benzoyloxyl radical in DNA damage mediated by benzoyl peroxide. Chem Res Toxicol 4: 223-8, 1991.
24. Hazlewood C, Davies MJ. Benzoyl peroxide-induced damage to DNA and its components: Direct evidence for the generation of base adduct, sugar radicals and strand breaks. Arch Biochem Biophys 332: 79-91, 1996.
25. Hayashi M, Kishi M, Sofuni T et al. Micronucleus tests in mice on 39 food additives and eight miscellaneous chemicals. Food Chem Toxicol 26: 487-500, 1988.
26. Hayashi M, Sutou S, Shimada H et al. Difference between intraperitoneal and oral gavage application in the micronucleus test. The 3rd collaborative study by CSGMT/JEMS. MMS. Collaborative Study Group for the Micronucleus Test/Mammalian Mutagenesis Study Group of the Environmental Mutagen Society of Japan Mutat Res 223: 329- 44, 1989.
27. Nakajima M, Kitazawa M, Oba K et al. Effect of route of administration in the micronucleus test with potassium bromate. Mutat Res 223: 399-402, 1989.
28. Sai K, Hayashi M, Takagi A et al. Effects of antioxidants on induction of micronuclei in rat peripheral blood reticulocytes by potassium bromate. Mutat Res 269: 113-8, 1992.
29. Robbiano L, Carrozzino R, Puglia CP et al. Correlation between induction of DNA fragmentation and micronuclei formation in kidney cells from rats and humans and tissue-specific carcinogenic activity. Toxicol Appl Pharmacol 161: 153-9, 1999.
30. Liu Q, Jiao QC, Huang XM et al. Genotoxicity of drinking water from Chao Lake. Environ Res 80: 127-31, 1999.
31. Babich H, Zuckerbraun HL, Wurzburger BJ et al. Benzoyl peroxide cytotoxicity evaluated in vitro with the human keratinocytes cell line, RHEK-1. Toxicology 106: 187-96, 1996.
32. Cartwright RA, Hughes BR, Cunliffe WJ. Malignant melanoma, benzoyl peroxide and acne: A pilot epidemiological casecontrol investigation. Br J Dermatol 118: 239-42, 1988.
33. Hogan DJ, To T, Wilson ER et al. A study of acne treatments as risk factors for skin cancer of the head and neck. Br J Dermatol 125: 343-8, 1991.
34. Slaga TJ, Klein-Szanto AJ, Triplett LL et al. Skin tumorpromoting activity of benzoyl peroxide, a widely used free radical-generating compound. Science 213: 1023-5, 1981.
35. Odukoya O, Shklar G. Initiation and promotion in experimental oral carcinogenesis. Oral Surg Oral Med Pathol 58: 315-20, 1984.
36. Kurokawa Y, Takamura N, Matsushima Y et al. Studies on the promoting and complete carcinogenic activities of some oxidizing chemicals in skin carcinogenesis. Cancer Let 24: 299- 304, 1984.
37. Kraus AL, Munro IC, Orr JC et al. Benzoyl peroxide: An integrated human safety assessment for carcinogenicity. Regulatory Toxicology and Pharmacology 21: 87-107, 1995.
38. Qiu C, Fu F, Gao Q et al. The function of benzoyl peroxide in the induction of syrian golden hamster tongue carcinoma by chemical carcinogen. Hua Xi Kou Qiang Yi Xue Za Zhi, 18: 291- 3, 2000.
39. Bhasin G, Kauser H, Athar M. Free radical generating agents lead to the rapid progression of benign skin tumors to carcinoma in iron-overloaded mice. Arch Toxicol 78: 139-146, 2004.
40. Lawrence NJ, Barkinson EK, Emmerson A. Benzoyl peroxide interferes with metabolic co-operation between cultured human epidermal keratinocytes. Carcinogenesis 5: 419-21, 1984.
41. Hu J, Cotgreave IA. Glutathione depletion potentiates 12- Otetradecanoyl phorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication in WB-F344 rat liver epithelial cells: Relationship to intracellular oxidative stres. 1995. Chem Biol Interact 95: 291-307, 1995.
42. Jansen LA, Jongen WM. The use of initiated cells as a test system for the detection of inhibitors of gap junctional intercellular communication. Carcinogenesis 17: 333-9, 1996.
43. Jansen LA, Mesnil M, Jongen WM. Inhibition of gap junctional intercellular communication and delocalization of the cell adhesion molecule e-cadherin by tumor promoters. Carcinogenesis 17: 1527-31, 1996.
44. Budunova IV, Carbajal S, Slaga TJ. Effect of diverse tumor promoters on the expression of gap-junctional proteins connexin (Cx)26, Cx31.1 and Cx43 in SENCAR mouse epidermis. Mol Carcinog 15: 202-14, 1996.