Related Experiment Video
Updated: Aug 17, 2026
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Aflatoxin B1-induced DNA adduct formation in murine kidney and liver
Pawel Jaruga1, Vladimir L Vartanian2, Irina G Minko2
1Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
Abstract:
Aflatoxicosis is a life-threatening nephrotoxic condition arising from eating foods highly contaminated with aflatoxin-producing molds. Additionally, chronic aflatoxin exposures are linked to enhanced hepatocellular carcinomas. Using recent advances in mass spectrometry for the detection of aflatoxin B1 (AFB1) DNA adducts, we present data which show generation of these adducts in the kidney, albeit at ≈ 100-fold lower levels than in the liver of the same animal. This result is consistent with tissue-specific differences in the expression of cytochrome P450s implicated in the activation of AFB1. Although the mechanisms underlying aflatoxin-induced nephrotoxicity had been postulated to be driven by the generation of high levels of reactive oxygen species, measurement of oxidatively-induced DNA base damage did not reveal evidence for genotoxic induction of these lesions. Overall, this investigation provides evidence of the formation of aflatoxin-specific adducts in kidney tissue and challenges the hypothesis of acute aflatoxin exposures generating reactive oxygen-mediated DNA damage.
Insights
Aflatoxin B1 DNA adducts form in kidneys, but at lower levels than in the liver. This study challenges the idea that reactive oxygen species drive acute aflatoxin-induced kidney damage.
Area of Science:
- Toxicology
- Molecular Biology
- Biochemistry
Background:
- Aflatoxicosis, caused by aflatoxin ingestion, is a severe condition affecting the kidneys and liver.
- Chronic exposure to aflatoxins is associated with an increased risk of liver cancer.
- The exact mechanisms of aflatoxin-induced nephrotoxicity are not fully understood.
Purpose of the Study:
- To investigate the formation of aflatoxin B1 (AFB1) DNA adducts in kidney tissue.
- To compare AFB1 adduct levels in the kidney and liver.
- To evaluate the role of reactive oxygen species in AFB1-induced nephrotoxicity.
Main Methods:
- Utilized advanced mass spectrometry techniques to detect AFB1 DNA adducts.
- Quantified AFB1 adducts in both kidney and liver tissues from exposed animals.
- Measured oxidatively-induced DNA base damage to assess reactive oxygen species involvement.
Main Results:
- AFB1 DNA adducts were detected in kidney tissue, though approximately 100-fold lower than in the liver.
- Tissue-specific differences in cytochrome P450 expression likely influence AFB1 activation.
- No evidence of genotoxic DNA base damage from reactive oxygen species was found, challenging existing hypotheses.
Conclusions:
- AFB1 does form DNA adducts in the kidney, indicating direct interaction.
- The lower adduct levels in the kidney suggest differential metabolic activation compared to the liver.
- The findings do not support reactive oxygen species as the primary mechanism for acute aflatoxin-induced nephrotoxicity.
More Related Videos
12:15Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
08:25Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
Published on: June 5, 2020
Related Concept Videos
01:08Nucleotide Excision Repair
01:25Bioactivation and Tissue Toxicity
01:30Spontaneous and Induced Mutations