Biochemical effects of veterinary antibiotics on proliferation and cell cycle arrest of human HEK293 cells.
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, p21(Waf1/Cip1) and Rb protein, which are crucial in the G1-S transition. The activation of p21(Waf1/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.
School of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju, 500-712, Korea.
Hyeon Young
HY
Kim
Ki-Tae
KT
Kim
Sang Don
SD
Kim
D000658:Amoxicillin / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002751:Chlortetracycline / Q000009:adverse effects; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004781:Environmental Exposure / Q000032:analysis*; D057809:HEK293 Cells; D006801:Humans; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D015645:Tylosin / Q000009:adverse effects; D015854:Up-Regulation
D000900:Anti-Bacterial Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D000658:Amoxicillin; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D002751:Chlortetracycline; D015645:Tylosin