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Published on: April 26, 2018
Metformin's performance in in vitro and in vivo genetic toxicology studies
Juliane R Sant'Anna1, Joana Paula R S Yajima, Lúcia J Rosada
1Laboratório de Genética de Microorganismos e Mutagênese, Departamento de Biotecnologia, Genética e Biologia Celular, Universidade Estadual de Maringá, 87020-900, Maringá, PR, Brazil.
Abstract:
Metformin is a hypoglycemiant drug prescribed for the treatment and control of the type 2 diabetes mellitus. Recently, the potential efficacy of this antidiabetic drug as an anticancer agent has been demonstrated in various mammalian cancer cells. This report evaluates the mutagenic as well as the recombinogenic potentials of the metformin drug in therapeutically relevant plasma concentrations (12.5 µM, 25.0 µM or 50.0 µM). Since the loss of heterozygosity is a process associated with carcinogenesis, the recombinogenic potential of such a drug was evaluated by the homozygotization assay using a heterozygous diploid strain of Aspergillus nidulans. The homozigotization indices (HI) for the genetic markers from the metformin-treated diploids were not statistically different from the negative control (non-treated diploids). For the first time, this indicated a lack of recombinogenic activity of the antidiabetic drug. The mutagenic potential of the metformin drug was evaluated by the chromosome aberrations and the micronuclei tests in human lymphocytes cultures. The metformin drug did not show any significant increase either in the numerical or in the structural chromosome aberrations and did not affect significantly the mitotic index when compared to the negative control. In the in vitro micronucleus test, the drug did not increase the number of micronuclei or nuclear buds when compared with the negative control. The data in this study suggest that the metformin drug is not a secondary cancer inducer, since it has neither showed recombinogenic nor mutagenic activities when used in pharmacological concentrations.
Insights
Metformin, used for type 2 diabetes, was tested for cancer-causing effects. Studies show metformin is not mutagenic or recombinogenic at therapeutic concentrations, suggesting it does not induce secondary cancers.
Area of Science:
- Pharmacology
- Genetics
- Oncology
Background:
- Metformin is a primary treatment for type 2 diabetes mellitus.
- Emerging research suggests metformin's potential anticancer properties in cell studies.
- This study investigates metformin's safety regarding genotoxicity and carcinogenicity.
Purpose of the Study:
- To evaluate the mutagenic and recombinogenic potentials of metformin.
- To determine if metformin induces genetic damage at therapeutic plasma concentrations.
- To assess metformin's risk as a secondary cancer inducer.
Main Methods:
- Recombinogenic potential assessed using a homozygotization assay in Aspergillus nidulans.
- Mutagenic potential evaluated via chromosome aberration and micronucleus tests in human lymphocytes.
- Drug concentrations used were 12.5 µM, 25.0 µM, and 50.0 µM.
Main Results:
- Metformin showed no statistically significant increase in homozygotization indices compared to controls.
- No significant increase in numerical or structural chromosome aberrations was observed.
- Metformin did not elevate micronuclei or nuclear buds in human lymphocytes.
Conclusions:
- Metformin demonstrated a lack of recombinogenic activity in the Aspergillus nidulans assay.
- Metformin exhibited no mutagenic activity in human lymphocyte tests.
- Findings suggest metformin is not a secondary cancer inducer at pharmacological concentrations.
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