Antimutagen

Antimutagens are the agents that interfere with the mutagenicity of a substance. ^[1] The interference can be in the form of prevention of the transformation of a promutagenic compound into actual active mutagen, inactivation, or otherwise the prevention of Mutagen-DNA reaction. ^[2]

Antimutagens can be classified into: Desmutagens, that inactivate the chemical interactions before the mutagen attacks the genes and Bio-antimutagens, that stop the mutation process once after the genes are damaged by mutagens. ^[2] There are a number of naturally occurring anti-mutagens that show their efficient action. ^{[3] [4] [5]}

Examples of antimutagens

Micronutrients

Nutrients such as vitamins and minerals are examples of micronutrients that are necessary for the proper maintenance of metabolism homeostasis in humans and other species. Micronutrients are also pointed to perform a role in genome stability acting as potential antimutagenic agents ^[6] (see the examples below):

• Carotenoids: Induction of single break DNA repair by a rejoining mechanism and elimination of 8-oxoguanine which is usually resulted from oxidative stress in cells;
• Vitamins:^{[ citation needed ][ clarification needed ]} Can induce cell programmed death via activation of p53 and increase of cellular mechanisms against strand breaks;
• Flavonoid polyphenolics: Found to perform antimutagenic activity through the increase of OGG1 expression, which is an enzyme responsible to remove 8-oxoguanine a mutagenic product created after cell's exposure to oxidative stress; Increase of single break repair by rejoining and induction of genes related to base and nucleotide excision repair such as XPA and XPC;
• Selenium: Induces programmed cell death via many signalling pathways as well as protects the cells against cell damage caused by oxidative stress.
• Magnesium: Essentially necessary for the process of nucleotide excision repair where in cells treated in absence of this micronutrient the repair was impaired. ^[7]

UV blockers

Main article: UV filter

Sunscreens are products commonly known by their capacity of protecting skin against sunburns. The active components present in sunscreens can vary, thus affecting the mechanism of protection against UV light, which can be done through absorption or reflection of UV energy. ^[8] As UV light can cause mutations by DNA damaging, sunscreen is considered an antimutagenic compound as it blocks the action of the UV light to induce mutagenesis in cells, basically the sunscreen inhibit the penetration of the mutagen. ^[9]

Tumor suppressor genes

Main article: Tumor suppressor gene

These genes have the function of protecting cells against tumor-like behaviour, such as higher proliferative rates and unlimited growth. It is common to find those genes down regulated or even inactivated in tumor cells. Thus, tumor suppressor genes can be recognized as antimutagenic agents. ^[10]

• TP53: This gene encodes for the p53 protein, which is known to act on the apoptotic signalling pathway and is also described to be important in the break excision repair of cells that had their DNA damaged. p53 is a transcription factor that is involved in the transcription of many genes, some of which related to the process of cell response against DNA damage. Some types of cancer show a high prevalence of lower or even absent levels of expression of this protein, sustaining its importance against mutagenesis. ^[11]
• PTEN: PTEN is another gene considered a tumor suppressor and acts through the inactivation of the PI3K-AKT pathway that leads to cell growth and survival. In other words, this gene is important to cause the cell growth arrest avoiding posterior effects and consequences of mutagenesis. ^[12]

References

1. "The database and ontology of Chemical Entities of Biological Interest". EMBL-EBI, European Molecular Biology Laboratory, Wellcome Trust Genome Campus.
2. Kada, Tsuneo; Inoue, Tadashi; Ohta, Toshihiro; Shirasu, Yasuhiko (1986). "Antimutagens and their Modes of Action". Antimutagenesis and Anticarcinogenesis Mechanisms. Vol. 39. pp. 181–196. doi:10.1007/978-1-4684-5182-5_15. ISBN   978-1-4684-5184-9. PMID   3533041.{{cite book}}: |journal= ignored (help)
3. Renner, H.W.; Münzner, R. (April 1991). "The possible role of probiotics as dietary antimutagens". Mutation Research Letters. 262 (4): 239–245. doi:10.1016/0165-7992(91)90090-q. PMID   1708108.
4. Mitscher, Lester A.; Telikepalli, Hanumaiah; McGhee, Eva; Shankel, Delbert M. (1996-02-19). "Natural antimutagenic agents". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 350 (1): 143–152. Bibcode:1996MRFMM.350..143M. doi:10.1016/0027-5107(95)00099-2. PMID   8657175.
5. E. Wall, Monroe (1992). "Antimutagenic Agents from Natural Products". Journal of Natural Products. 55 (11): 1561–1568. Bibcode:1992JNAtP..55.1561W. doi:10.1021/np50089a002. PMID   1479376.
6. Arigony, AL; de Oliveira, IM; Machado, M; Bordin, DL; Bergter, L; Prá, D; Henriques, JA (2013). "The influence of micronutrients in cell culture: a reflection on viability and genomic stability". BioMed Research International. 2013 597282. doi: 10.1155/2013/597282 . PMC   3678455 . PMID   23781504.
7. Collins, AR; Azqueta, A; Langie, SA (April 2012). "Effects of micronutrients on DNA repair". European Journal of Nutrition. 51 (3): 261–79. doi:10.1007/s00394-012-0318-4. PMID   22362552. S2CID   23866597.
8. Maslin, DL (November 2014). "Do suncreens[sic] protect us?". International Journal of Dermatology. 53 (11): 1319–23. doi: 10.1111/ijd.12606 . PMID   25208462.
9. De Flora, S (18 June 1998). "Mechanisms of inhibitors of mutagenesis and carcinogenesis". Mutation Research. 402 (1–2): 151–8. Bibcode:1998MRFMM.402..151D. doi:10.1016/s0027-5107(97)00292-3. PMID   9675264.
10. Hausman, Geoffrey M. Cooper ; Robert E. (2003). The cell (3 ed.). Washington, DC: ASM Press [u.a.] ISBN   978-0-87893-214-6.
11. Zurer, I; Hofseth, LJ; Cohen, Y; Xu-Welliver, M; Hussain, SP; Harris, CC; Rotter, V (January 2004). "The role of p53 in base excision repair following genotoxic stress". Carcinogenesis. 25 (1): 11–9. doi: 10.1093/carcin/bgg186 . PMID   14555612.
12. Song, MS; Salmena, L; Pandolfi, PP (4 April 2012). "The functions and regulation of the PTEN tumour suppressor". Nature Reviews. Molecular Cell Biology. 13 (5): 283–96. doi:10.1038/nrm3330. PMID   22473468. S2CID   28514977.

Further reading

• Ramel, Class; et al. (1986). "Inhibitors of mutagenesis and their relevance to carcinogenesis: Report by ICPEMC expert group on antimutagens and desmutagens". Mutation Research/Reviews in Genetic Toxicology. 168 (1): 47–65. doi:10.1016/0165-1110(86)90021-7. PMID   3520303.
• Stavric, B (1994). "Antimutagens and anticarcinogens in foods". Food and Chemical Toxicology. 32 (1): 79–90. doi:10.1016/0278-6915(84)90040-1. PMID   8132169.
• Hartman, Philip E.; Shankel, Delbert M. (1990). "Antimutagens and anticarcinogens: a survey of putative interceptor molecules". Environmental and Molecular Mutagenesis. 15 (3): 145–182. Bibcode:1990EnvMM..15..145H. doi:10.1002/em.2850150305. PMID   2185012. S2CID   23902598.