Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro

Toxicology Letters
Kathleen BoehmeStefan O Mueller

Abstract

The current genotoxicity tests of the standard in vitro battery, especially those using mammalian cells, are limited by their low specificity and highlight the importance of new in vitro tools. This study aimed to evaluate the suitability of HepG2 cells for assaying mutagens and promutagens. We determined P53 activity as surrogate genotoxicity endpoint in HepG2 cells. Our results revealed a significant P53-induction by actinomycin D, methyl methanesulfonate and etoposide. Prior to the investigation of promutagens we characterized HepG2 cells by analyzing the expression of 45 genes involved in xenobiotic metabolism and measuring the activity of selected Cytochrome-P450 (CYP) enzymes. We determined a limited metabolic capacity prompting us to employ a co-treatment with rat liver S9 as metabolic activation system (MAS) for promutagens. While cyclophosphamide showed an elevation of activated P53 in the presence of S9, 7,12-dimethylbenz[a]anthracene and aflatoxin B(1) responded without the MAS. Inhibition of cellular CYP3A4 or CYP1A/1B suppressed the aflatoxin B(1)- and dimethylbenz[a]anthracene-mediated P53 response, respectively, indicating that HepG2 cells are capable of metabolizing these compounds in a CYP1A/B/3A4-dependent man...Continue Reading

References

Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·B BressacM Ozturk
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·H M Sobell
Jul 1, 1988·Chemical Research in Toxicology·S C ChengA Dipple
Jan 1, 1988·Environmental and Molecular Mutagenesis·E ZeigerK Mortelmans
Mar 1, 1995·Chemical Research in Toxicology·Y F UengF P Guengerich
Jan 16, 1999·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·O PelkonenH Raunio
Jan 20, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·K R Hande
Sep 30, 1999·Environmental Health Perspectives·P J Duerksen-HughesO Ozcan
Jul 25, 2000·Toxicology Letters·G Boos, H Stopper
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 4, 2003·Nature Reviews. Cancer·Patrick Chène
Mar 5, 2003·Teratogenesis, Carcinogenesis, and Mutagenesis·A P A GuimarãesE T Sakamoto-Hojo
Mar 12, 2003·The Pharmacogenomics Journal·H-J XieA Rane
Jun 7, 2003·Toxicology and Applied Pharmacology·Esther F A BrandonJan H M Schellens
Jul 18, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan WilkeningAugustinus Bader
Dec 20, 2003·Current Drug Metabolism·Hongbing Wang, Masahiko Negishi
Mar 31, 2004·Journal of Applied Toxicology : JAT·Ramesh C ChoudhuryPrajyoti Sahu
Jun 19, 2004·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·N J Hewitt, P Hewitt
Apr 19, 2005·Archives of Pharmacal Research·Changjiang XuAh-Ng Tony Kong
Mar 22, 2006·Oncogene·C Rodriguez-Antona, M Ingelman-Sundberg
Mar 3, 2007·Nature Reviews. Cancer·Thorsten Stiewe
Jul 20, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Walter M A Westerink, Willem G E J Schoonen
Jan 3, 2009·Toxicology and Applied Pharmacology·L RichertS O Mueller
Jul 4, 2009·Toxicology and Applied Pharmacology·Mario T SchellenbergerClaude P Muller

❮ Previous
Next ❯

Citations

Apr 30, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kathleen BoehmeStefan O Mueller
Aug 10, 2011·Mutation Research·D J SmartA M Lynch
Mar 23, 2011·Toxicology and Applied Pharmacology·M G L ElferinkG M M Groothuis
Oct 10, 2013·Environmental and Molecular Mutagenesis·Laure KhouryMarc Audebert
May 9, 2012·Mutation Research·Célia MartinsAntónio S Rodrigues
Jan 13, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Samuel LiebelFrancisco Filipak Neto
Aug 8, 2014·ISRN Toxicology·C UraniL Gribaldo
Jun 14, 2017·The Pharmacogenomics Journal·D M GattiG A Churchill
Jul 25, 2019·Journal of Biochemical and Molecular Toxicology·Mohammad S AkhterNektarios Barabutis
Sep 3, 2020·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Heather Wallace
Apr 20, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Mona S AlwhibiAhmed S Sultan
May 14, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Clémence BudinLaura Soler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aspergillosis

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Aspergillosis (ASM)

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Related Papers

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Walter M A Westerink, W G Schoonen
Xenobiotica; the Fate of Foreign Compounds in Biological Systems
N J Hewitt, P Hewitt
Drug Metabolism and Disposition : the Biological Fate of Chemicals
Stefan WilkeningAugustinus Bader
© 2021 Meta ULC. All rights reserved