Mutagen influence with different mechanisms of action on DNA global methylation in human whole-blood lymphocytes in vitro

• Published in: Russian journal of genetics Vol. 49; no. 7; pp. 765 - 770
• Main Authors: Smirnikhina, S. A., Voronina, E. S., Strelnikov, V. V., Tanas, A. S., Lavrov, A. V.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-07-2013
• Subjects: Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; Cancer; Human Genetics; Microbial Genetics and Genomics; Lymphocyte Culture; Global Methylation Level; Global Methylation; Comet Assay; Methylation Level
• ISSN: 1022-7954; 1608-3369
• DOI: 10.1134/S1022795413060124

Data that support the evidence of mutagens known to cause epigenetic abnormalities that could potentially result in genomic instability and the development of cancer rather than to modifications in the human genome at the gene and chromosomal levels only. The level of global methylation in human lymphocytes in vitro caused by exposure to two mutagens with different mechanisms of action, i.e., dioxidine and methyl methanesulphonate (MMS), was demonstrated in the present study. Global methylation was assessed by methyl-sensitive comet assay. An increase in the level of global methylation to 45.64% was revealed during culturing with dioxidine in a concentration of 0.01 mg/mL (
p
< 0.001), while the addition of dioxidine in a concentration of 0.1 mg/mL resulted in a decreased level of methylation up to 42.31% (
p
< 0.001). The addition of MMS in concentrations of 0.0025 and 0.01 mg/mL resulted in minor but significant modifications (
p
< 0.05) of the global methylation level ranged within natural variations in global methylation. Accordingly, the addition of dioxidine in the concentration of 0.1 mg/mL might cause genomic instability and might be considered a potential carcinogen.