Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells

Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells

Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for r...

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Bibliographic Details
Published in:Genetics and molecular biology Vol. 35; no. 1; pp. 153 - 158
Main Authors: Amador, Rubem R, Longo, João Paulo Figueiró, Lacava, Zulmira G, Dórea, José G, Almeida Santos, Maria de Fátima M
Format: Journal Article
Language:English
Published: Brazil Sociedade Brasileira de Genética 01-01-2012
Subjects:
BIOCHEMISTRY & MOLECULAR BIOLOGY
chromosome aberration
DNA damage
GENETICS & HEREDITY
metformin
metformin
DNA damage
chromosome aberration
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Summary:Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays) and in mice (micronucleus assays). Concentrations of 114.4 μg/mL and 572 μg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 μg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.
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Associate Editor: Daisy Maria F. Salvadori
ISSN:1415-4757
1678-4685
1678-4685
DOI:10.1590/s1415-47572011005000060