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

Abstract

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.

Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells

“…Metformin was highly cytotoxic under glucose-depleted, but not hypoxic conditions ( Fig 1A ). This result is consistent with previous findings showing the selective cytotoxicity of metformin when combined with the hypoglycemia-mimicking agent 2-deoxy-D-glucose [ 5 , 14 ]. Thus, glucose deprivation augments the cytotoxic effects of metformin.…”

Potential Applications of Sos-GFP Biosensor to in Vitro Rapid Screening of Cytotoxic and Genotoxic Effect of Anticancer and Antidiabetic Pharmacist Residues in Surface Water

“…Previous studies showed that recA promoter was induced by known genotoxins and selected anticancer drugs [Ptitsyn et al 1997, Kostrzyńska et al 2002, Zaslaver et al 2004 According to the results obtained in our experi-ment M in simultaneous co-administration with CP was shown to modulate and dramatically increase the reactivity of recA promoter in relation to separate bacteria treatment with CP and M. Amador et. al.…”

Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients

“…3). In vitro results indicate that chronic exposure to metformin and glimepiride may be potentially genotoxic (Amador et al, 2011). In vivo studies by Gurbuzel et al (2014) state the potential genotoxic effect of glimepiride in Drosophila.…”