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

Genetics and Molecular Biology

Rubem R. Amador²  João Paulo Figueiró Longo²  Zulmira G. Lacava²  José G. Dórea¹  Maria De Fátima M. Almeida Santos² 

[1] ,Universidade de Brasília Instituto de Ciências Biológicas Departamento de Genética e Morfologia

关键词: metformin;    DNA damage;    chromosome aberration;   

DOI  :  10.1590/S1415-47572011005000060

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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