Cell-Based Genotoxicity Testing

2009 ◽  
pp. 85-111 ◽  
Author(s):  
Georg Reifferscheid ◽  
Sebastian Buchinger
Keyword(s):  
2005 ◽  
Vol 36 (9) ◽  
pp. 1710-1717 ◽  
Author(s):  
Nevena Stojicic ◽  
David Walrafen ◽  
Christa Baumstark-Khan ◽  
Elke Rabbow ◽  
Petra Rettberg ◽  
...  

Author(s):  
Ulrike Kammann ◽  
Markus Bunke ◽  
Hans Steinhart ◽  
Norbert Theobald

2008 ◽  
Vol 71 (13-14) ◽  
pp. 930-935 ◽  
Author(s):  
Angelika Flieger ◽  
Klaus Golka ◽  
Harald Schulze ◽  
Wolfram Föllmann

Author(s):  
Farhana Masood ◽  
Reshma Anjum ◽  
Masood Ahmad ◽  
Abdul Malik

2020 ◽  
Vol 175 (2) ◽  
pp. 251-265 ◽  
Author(s):  
Xilin Li ◽  
Si Chen ◽  
Xiaoqing Guo ◽  
Qiangen Wu ◽  
Ji-Eun Seo ◽  
...  

Abstract Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress 1 of 8 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using 2 prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared with EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared with EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.


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