The purpose of this study was to examine the effects of veterinary antibiotics, including amoxicillin (AMX), chlortetracycline (CTC) and tylosin (TYL), on the biochemical mechanism of human embryonic kidney cells (HEK293). CTC and TYL inhibited HEK293 cell proliferation, in both time- and dose-dependent manners, and changed the cell morphology; whereas, AMX showed no cytotoxic effects. The cell cycle analysis of CTC and TYL revealed G1-arrest in HEK293 cells. Western blot analysis also showed that CTC and TYL affected the activation of DNA damage responsive proteins, as well as cell cycle regulatory proteins, such as p53, p21Waf1/Cip1 and Rb protein, which are crucial in the G1-S transition. The activation of p21Waf1/Cip1 was significantly up-regulated over time, but there was no change in the level of CDK2 expression. The results of this study suggest that veterinary antibiotics, even at low level concentrations on continuous exposure, can potentially risk the development of human cells.
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Ankley GT, Brooks BW, Huggett DB, Sumpter JP (2007) Repeating history: pharmaceuticals in the environment. Environ Sci Technol 41:8211–8217
Babín M, Boleas S, Tarazona JV (2005) In vitro toxicity of antimicrobials on RTG-2 and RTL-W1 fish cell lines. Environ Toxicol Pharmacol 20:125–134
Bacon JA, Linseman DA, Raczniak TJ (1990) In vitro cytotoxicity of tetracyclines and aminoglycosides in LLC-PK1, MDCK and Chang continuous cell lines. Toxicol In Vitro 4:384–388
Boxall ABA, Fogg LA, Blackwell PA, Kay P, Pemberton EJ (2001) Review of veterinary medicines in the environment. R&D Technical Report, Bristol, UK, UK Environment Agency
Eisenbrand G, Pool-Zobel B, Baker V, Balls M, Blaauboer BJ, Boobis A, Carere A, Kevekordes S, Lhuguenot JC, Pieters R, Kleiner J (2002) Methods of in vitro toxicology. Food Chem Toxicol 40:193–236
Elledge SJ (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274:1664–1672
Erickson BE (2002) Analyzing the ignored environmental contaminants. Environ Sci Technol 36:140A–145A
Hengstschläger M, Braun K, Soucek T, Miloloza A, Hengstschläger-Ottnad E (1999) Cyclin-dependent kinases at the G1-S transition of the mammalian cell cycle. Mutat Res Rev Mutat 436:1–9
Hirsch R, Ternes T, Haberer K, Kratz KL (1999) Occurrence of antibiotics in the aquatic environment. Sci Total Environ 225:109–118
Jones OA, Lester JN, Voulvoulis N (2005) Pharmaceuticals: a threat to drinking water? Trends Biotechnol 23:163–167
Kim Y, Jung J, Kim M, Park J, Boxall ABA, Choi K (2008) Prioritizing veterinary pharmaceuticals for aquatic environment in Korea. Environ Toxicol Pharmacol 26:167–176
Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: A national reconnaissance. Environ Sci Technol 36:1202–1211
Laville N, Aït-Ässa S, Gomez E, Casellas C, Porcher JM (2004) Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Toxicology 196:41–55
Nurse P (2000) A long twentieth century of the cell cycle and beyond. Cell 100:71–78
Pomati F, Castiglioni S, Zuccato E, Fanelli R, Vigetti D, Rossetti C, Calamari D (2006) Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells. Environ Sci Technol 40:2442–2447
Sherr CJ, Roberts JM (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9:1149–1163
Webb S, Ternes T, Gibert M, Olejniczak K (2003) Indirect human exposure to pharmaceuticals via drinking water. Toxicol Lett 142:157–167
This research was supported by “Innovative Technology of Ecological Restoration” project at GIST.
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Kim, H.Y., Kim, KT. & Kim, S.D. Biochemical Effects of Veterinary Antibiotics on Proliferation and Cell Cycle Arrest of Human HEK293 Cells. Bull Environ Contam Toxicol 89, 234–239 (2012). https://doi.org/10.1007/s00128-012-0695-7
- Veterinary antibiotics
- HEK293 cells
- Cell damage
- Cell cycle arrest