Metformin's performance in in vitro and in vivo genetic toxicology studies.
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.
["Sant'Anna|Juliane R|JR|", 'Yajima|Joana Paula R S|JP|', 'Rosada|Lúcia J|LJ|', 'Franco|Claudinéia C S|CC|', 'Prioli|Alberto J|AJ|', 'Della-Rosa|Valter A|VA|', 'Mathias|Paulo Cezar F|PC|', 'Castro-Prado|Marialba A A|MA|']
D000328:Adult D001233:Aspergillus nidulans D002842:Chromatids D002869:Chromosome Aberrations D020090:Chromosome Segregation D033481:Chromosomes, Mammalian D004171:Diploidy D005260:Female D006238:Haploidy D006579:Heterozygote D006720:Homozygote D006801:Humans D008214:Lymphocytes D008297:Male D008687:Metformin D015162:Micronucleus Tests D008940:Mitotic Index D009153:Mutagens D055815:Young Adult
mutagenicity homozygotization assay Aspergillus nidulans chromosome aberrations Genotoxicity micronucleus assay