Related Experiment Video

Updated: Jun 17, 2026

Automation of Bio-Atomic Force Microscope Measurements on Hundreds of C. albicans Cells
09:27

Automation of Bio-Atomic Force Microscope Measurements on Hundreds of C. albicans Cells

Published on: April 2, 2021

Analysis of the mutations induced by conazole fungicides in vivo

Jeffrey A Ross1, Sharon A Leavitt

  • 1Carcinogenesis Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Ross.jeffrey@epa.gov

Mutagenesis
|January 13, 2010
PubMed

Insights

Tumorigenic conazole fungicides, triadimefon and propiconazole, induce mutations in mouse liver by accumulating reactive metabolites. Non-tumorigenic myclobutanil did not show mutagenic effects in this study.

Area of Science:

  • Toxicology
  • Genetics
  • Molecular Biology

Background:

  • Conazole fungicides like triadimefon and propiconazole are tumorigenic in mouse liver.
  • These fungicides have demonstrated mutagenic potential in vivo using the Big Blue transgenic mutation assay.
  • The non-tumorigenic conazole myclobutanil serves as a control for mutagenicity.

Purpose of the Study:

  • To investigate the mode of action by which tumorigenic conazoles induce mutations in mouse liver.
  • To differentiate the mutagenic mechanisms of tumorigenic versus non-tumorigenic conazoles.
  • To analyze DNA mutation patterns to understand conazole-induced genotoxicity.

Main Methods:

  • DNA sequencing of mutants from mice treated with triadimefon, propiconazole, myclobutanil, or control diet.
  • Calculation of relative dinucleotide mutabilities (RDMs) for each treatment group.
  • Multivariate statistical analyses including hierarchical clustering and principal component analysis (PCA) of RDM values.

Main Results:

  • Hierarchical clustering and partitioning around medoids analysis segregated the tumorigenic conazoles (triadimefon, propiconazole) from the non-tumorigenic conazole (myclobutanil) and controls based on RDM patterns.
  • PCA revealed two components explaining 88.3% of the variability, further distinguishing the mutagenic effects.
  • Mutational profiles suggest that conazole-induced mutations are not due to clonal expansion of background mutations.

Conclusions:

  • The mutagenic effects of propiconazole and triadimefon are consistent with the accumulation of reactive electrophilic metabolic intermediates in the liver.
  • These findings support a specific mechanism of genotoxicity for tumorigenic conazoles.
  • Myclobutanil's lack of mutagenicity provides a contrast, highlighting the specific risks associated with certain conazole fungicides.

More Related Videos

Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae12:13

Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae

Published on: April 5, 2015

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

Related Concept Videos

In vitro Mutagenesis01:16

In vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.