Abstract
Mutation is the process leading to heritable changes in DNA caused mainly by internal and external factors. Recently, studies on mutagenic agents have been increased due to increasing in mutation-related disease. The antimutagenic effect is desired to prevent mutation on genes or to inactivate the mutagenic agent. It seems that the interest in antimutagenic substances displaying multiple mechanisms of action will be an important trend in the research and development of new antimutagenic compounds in the near future. Therefore, this chapter displays various possible mechanisms of action for antimutagenic agent and introduces different types of antimutagens, natural and synthetic, that are considered very important.
Keywords
- mutagenesis
- antimutagenic
- mechanism
- natural
- synthetic
- DNA
1. Introduction
Mutagenicity is the process of induction of permanent heritable changes in the DNA sequence of living systems [1]. It is caused mainly by the external factors, including chemical and physical agents, or can also occur spontaneously due to errors in DNA repair, replicationand recombination [2]. A number of mutagens have been recognized in our environment recently as many factors which modulate the toxic activities either in vitro or in vivo [3]. Agents contributing to mutagenesis in the environment could be from wide-spectrum applications of biocides in the agriculture, industrial sources, and other contaminants [3].
These mutagenic chemicals have severe drawbacks in humans such as cancer and various inherited diseases; therefore, it is important to detect such mutagenic agents precisely and rapidly and also look for solutions to combat them [2].
Natural occurring dietary antimutagens such as healthy protective foods such as fruits and vegetables could strongly counteract the deleterious effect of these mutagens [4]. Additionally, the World Health Organization (WHO) revealed that one-third of all cancer death incidences are preventable depending on the diet type especially health protective phytochemicals that provide an effective solution to these concerns [4]. The current chapter will present the mutagenic events and a brief compilation of the existing scientific findings either from dietary sources or synthetic agents that have the potential activity to combat the disorders caused by the mutagenic agents, putting in mind possible future perspectives and mechanism of antimutagenics [2].
2. Mechanisms of action
Several classes of antimutagenic compounds may be distinguished based on their mechanism of action as the following:
2.1 Antimutagens with antioxidant potency
Reactive oxygen species (ROS) are generated by many mutagens; therefore, the removal of reactive molecules is considered an important strategy in the process of antimutagenesis. It is reported that compounds with antioxidant propertiescan remove ROS before these molecules react with DNA, resulting in a mutation [5].
It was reported that the antigenotoxic effects of Lipoic acid (LA) (Figure 1) against mitomycin-C induced chromosomal aberrations, sister chromatid exchanges, and micronucleus formation was observed in human peripheral lymphocytes. Moreover, LA exhibits both anticlastogenic and antimutagenic activity [6].
2.2 Interaction with mutagen
A potential protective mechanism against mutagenesis is related to the direct chemical interaction between a mutagen and an antimutagenic compound before it induces DNA damage leading to the inhibition of their damaging activity. Sulfhydryl compounds, such as cysteine, can inactivate 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) (Figure 2) [7].
2.3 Antimutagen as blocking agents
The mechanism of action for this type of antimutagenics is to prevent mutagenic compounds from reaching target sites such as nucleophilic bichalcophenes (Figure 3). They might be able to bind to DNA and, therefore, protect genetic materials from electrophilic mutagenic agents [8].
2.4 Multifunctionally acting antimutagens
Various antimutagenic agents work through multiple mechanisms affording protection against several mutagens. Noteworthy, the ability of compounds to affect mutagens simultaneously in varied ways significantly enhances antimutagenic effectiveness. Hence, searching for such multifunctionally acting antimutagens is of great importance [9].
2.5 Desmutagenesis
This way of preventing induced cellular mutagenesis depends on mutagens that are inactivated before they can attack the DNA in vitro [3].
2.6 Bio-antimutagenesis
Damaged DNAusually requires fixation steps (e.g., DNAreplication and/or repair) before it can be expressed as stable and heritable mutant genes. Hence this mechanism relates to interference with some aspects of cellular DNA fixation processes working on reducing genetic damage in DNA [3].
3. Antimutagenic agents
Antimutagenic agents are able to combat the disorders caused by mutagens [10]. This group of agents includes both natural and synthetic compounds categories [1].
3.1 Natural antimutagenic agents
The antimutagenic effect of natural sources was investigated due to certain compounds in them or due to whole extract.
3.1.1 Isolated compounds
3.1.1.1 Cinnamaldehyde
It is the first naturally occurring organic antimutagen [11]; it has been involved in screening and chemical studies of such biologically active substances [12]. Antimutagenic action is attributed to either by a selective killing effect of cells which have premutation lesion of DNA via inhibition of the errorprone SOS repair system, or by enhancement of the error-free DNA repair system (Figure 4) [13].
3.1.1.2 Punicalagin (PC) and ellagic acid (EA)
Punicalagin is an ellagitannin found in the fruit peel of
3.1.1.3 Luteolin derivatives
Luteolin derivatives (luteolin 7-O-rutinoside, luteolin 7-O-glucoside, and luteolin 7-O-glucuronide) (Figure 6) are isolated from
3.1.1.4 Acetogenins
3.1.1.5 Pinocembrin and cardamonin
Pinocembrin and cardamonin (Figure 8) are found in Sozuku (Chinese drug from dried seed of
3.1.1.6 Harpagoside (HS)
It isa type of iridoid glycoside. HS (Figure 9) is considered as the main active component extracted from
3.1.1.7 Lycopene
Natural oleoresin is rich in lycopene (Figure 10), which was obtained from two types of tomato (Zedona and Gironda). The antimutagenic activity of oleoresin was tested against aflatoxin B1 (AFB1), and both varieties had awfully high antimutagenic potential against AFB1 (60–66%) [20].
3.1.1.8 Compounds extracted from Glycyrrhiza aspera root
The powdered extract of
3.1.2 Plant extract
3.1.2.1 Date palm fruit aqueous extract
It was found that
3.1.2.2 Maytenus ilicifolia and Peltastes peltatus extract
These two plants are both rich in compounds of the tanninand flavonoid groups and frequently employed in folk medicine. Antimutagenicity was determined against known mutagenic substances such as 4-oxide-1-nitroquinoline, NaN3, aflatoxin B1, 2-aminofluorene and 2-aminoanthracene, and 2-nitrofluorene using the
3.1.2.3 Citrus limonum fruit residues (CLFR)
Aqueous and acidified methanol extracts of CLFR were evaluated for their total phenolic contents and antioxidant and antimutagenic activities. Antimutagenic potential of the extracts was done by Ames test. The results supported that the extracts from CLFR were mutagenically safe due to its high phenolic content which can act as antioxidant and anitmutagenic [24].
3.1.2.4 Mimosa tenuiflora (MT) extract
The genotoxic effect of MT was investigated by using both micronucleus test and Ames test in
3.1.2.5 Albeofructus (ADA) extract
It is an extract of
3.1.2.6 Anemopsis californica (AC)
Although
3.1.2.7 Citrus sinensis and Citrus latifolia
The essential oils of
3.1.2.8 Heterotheca inuloides (HI) extract
The methanolic extract of HI reduced the mutagenicity of benzo[a]pyrene, norfloxacin, and 2-aminoanthracene. The antigenotoxic properties could be due to the antioxidant properties of component into extract such as catenanes, sterols, polyacetylenes, triterpenes, sesquiterpenes, flavonoids, and flavonoid glycosides [29].
3.1.2.9 Extracts of Acacia salicina
Literatures revealed that this extract displayed potent antioxidant and antimutagenic activities [30]. Also chloroform extract showed antimutagenic effect against both direct- and indirect-acting mutagens, as the extract may act as a blocking agent that is capable of influencing the activities of enzymes engaged in the metabolism of mutagens and carcinogens. Moreover, the tested extract displayed the ability to react directly with the mutagens electrophilic metabolite sand was capable of protecting against oxidative DNA damage [30].
3.1.2.10 Wheat bran
It was reported that wheat bran provides antimutagenic effects that related to the presence of the antioxidant phytic acid. It was demonstrated that phytic acid may intercept carcinogenic azoxymethane, inhibiting it even before it can damage DNA. Moreover, antioxidants included in wheat bran are able tomodulate DNA repair enzymes [31].
3.1.2.11 Vegetables
Activity was displayed by beets, chives, horseradish, onions, rhubarb, and spinach. All cruciferous vegetables showed strong to moderate antimutagenic activities, except Chinese cabbage, which displayed weak activity. Moderate antimutagenicity was found in green beans and tomatoes, whereas weak activities in egg plant, garden cress, many types of lettuces, leeks, mangold, cucumber, pumpkin, radish, and summer squash. However, some vegetables such as
Antimutagenic activity of many vegetable juiceswere earlier studied againstmutagenicity induced by2-amino-3-methyl[4,5-f]-quinoline (IQ), 2-amino-3,4dimethylimidazo[4,5-f] quinoline (MeIQ) or 2-amino3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx) in S.typhimurium TA98 and TA100 [33].
3.1.2.12 Fruits
Current research all over the world has focused on health protectiveproperties of fruits including antimutagenic potential of different fruittypes and their cultivars. Concerning apple fruit, its antioxidant and radioprotective properties were found to be better correlated with its antimutagenic effect [34]. Recently, copaiba, an exotic Brazilian fruit, possesses the antimutagenic potential of copaiba powder (dose of 100 mg/kg) showing great reduction of micronuclei [35].
3.1.2.13 Other sources
3.1.2.13.1 Ganoderma lucidum
3.1.2.13.2 Macro fungus
It was demonstrated that ethyl acetate extract of macro fungus showed the in vitro antimutagenic activity of
3.2 Synthetic antimutagenic agents
Synthetic antimutagens is another important trend in the area of antimutagenicity research.
3.2.1 Steroidal hormonal molecules
Bile acids have either a co- or an antimutagenic activity toward various direct- and indirect-acting mutagens [38]. It was reported that steroidal hormones could inhibit the genotoxicity of both direct- and indirect-acting mutagens [39]. For example, both ethinyl oestradiol and mestranol (Figure 12), which are synthetic derivatives of 3-estradiol largely used in contraceptive pills, are strong mutagenic inhibitors acting at nanomolar concentrations [39].
3.2.2 Gallic acid
It could act as a nucleophile to scavenge the electrophilic mutagens. It was implied that gallic acid (Figure 13) can bind or insert into the outer membrane transporters leading to the blockage of a mutagen that was transferred intothe cytosol [40]. One of the mutagenic substances that gallic acid affects is NaN3. It is widely used in agriculture, industry, and medicine, but it is a highly toxicsubstance. If sodium azide is found in the intracellular milieu, azide ions bind Fe3þ in hemoglobin and inhibit the respiratory chain of metabolism [41].
3.2.3 Tannic acid
The anticlastogenic effect of tannic acid (Figure 14) was studied
3.2.4 Synthesized β- aminoketones
Theantigenotoxic potential of two newly synthesized β-aminoketones such as2-{(4-bromophenyl)[(4-methylphenyl) amino] methyl} cyclohexanone and 2-{(4-chlorophenyl)[(4-methylphenyl) amino] methyl} cyclohexanone compounds was tested against the mutagenN-methyl-N-nitro-N-nitrosoguanidine (MNNG), acting by DNAmethylation (Figure 15) [9]. The antimutagenic potential of these compounds may be related to the inhibition of the production of O6-methylguanine, a product of MNNG that is related to its mutagenic effect. Both compounds also abolished mutagenesis induced by 9-AA that binds to DNA noncovalently by intercalation [43].
3.2.5 Phenolic agents
This category of antimutagenics acts against mutagens via either intracellularor extracellular mechanisms [44]. The extracellular mechanism showed interference with the cytochrome P450-mediated metabolismof these mutagens and the interaction with active mutagenicmetabolites [8]. Moreover, the antimutagenic potency of these compounds may be relatedto DNA protection from mutagens presenting electrophilicproperties [8].
Hydroxyphenyliminoligands and their metal complexes [Cu(II), Co(II), Ni(II) and Mn(II) complexes] of usnic acid (Figure 16) which is isolated from
New polymeric microspheres containing azomethine were designed and synthesized to evaluate their antimutagenic activity against NaN3, among of them; a new polymeric microspheres containing azomethine (Figure 17) which contains R = CH3 had potent antimutagenic effect against NaN3 [46].
Chitosan derivatives containing quaternary ammonium groups and di (tertbutyl) phenol (TBPh) (Figure 18) in the polymer side chain improved the antimutagenic efficiency of the polymer from 48 to 93% [47].
Hydrazone derivatives were synthesized to study their antioxidant and antimutagenic activity against 4-NPD and NaN3 in
3.2.6 Xanthones
The potential antimutagenic of xanthonesis attributed to different mechanisms, such as the rapid elimination of mutagens from bacteria; the interaction between antimutagens and the reactive intermediates of mutagens; and the influence on microsomal enzymes against direct mutagen 4-nitroquinoline-N-oxide (NQNO) (Figure 20) [49].
3.2.7 Indols
Novel polymeric-Schiff bases including indol (L1, L2, L3) (Figure 21) exhibited the antigenotoxic properties against sodium azide in human lymphocyte cells by micronuclei (MN) and sister chromatid exchange tests [50].
A series of indolizine derivatives have been synthesized to determine their antimutagenic activity, the indolizine derivative (Figure 22) had the highest activity [51].
3.2.8 Organoselenium
Scientists demonstrated that this series of compounds are protected against genotoxicity and oxidative stress induced by an indirect-acting mutagen CP [52]. This is attributed to effect of CP on DNA through its alkylating properties and free radicals production [53].
3.2.9 Bichalcophenes
The novel bichalcophenes significantly decreased the mutagenicity induced by two mutagens, namely, NaN3 and BP [54]. It was found that the antimutagenic potential of the compounds could be attributed to their antioxidant activity [55].
3.2.10 Others
New zerumbone-bicarbonyl analogues were synthesized to determine their antimutagenic activity against
Two newly synthesized oxadiazoles: 1,3-bis(5-benzylthio-1,3,4-oxadiazol-2-yl) benzene (M1) and 1,4-bis(5-benzylthio-1,3,4-oxadiazol-2-yl) benzene (M2) (Figure 25) were synthesized and studied in
Dihydrothienoquinoline derivatives were designed and synthesized to evaluate their antimutagenicity using Ames test. Several compounds showed good antimutagenicity. The results for compounds (Figure 26) were found to be statistically significant (P = 0) [58].
A series of novel azacrown ether Schiff bases have been synthesized, and they were investigated for their antimutagenic activities using the spot test and Ames test using strains TA1535, TA100, and TA97a of
References
- 1.
Słoczyńska K, Powroźnik B, Pękala E, Waszkielewicz AM. Antimutagenic compounds and their possible mechanisms of action. Journal of Applied Genetics. 2014; 55 (2):273-285 - 2.
Gautam S, Saxena S, Kumar S. Fruits and vegetables as dietary sources of antimutagens. Journal of Food Chemistry and Nanotechnology. 2016; 2 (3):97-114 - 3.
Kada T, Inoue T, Namiki M. Environmental Mutagenesis and Plant Biology. In: Environmental desmutagens and antimutagens. New York: Praeger; 1981. pp. 134-151 - 4.
Bode AM, Dong Z. Cancer prevention research—Then and now. Nature Reviews Cancer. 2009; 9 (7):508 - 5.
Tian YF, Hsieh CH, Hsieh YJ, Chen YT, Peng YJ, Hsieh PS. α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and β cell dysfunction. European Journal of Clinical Investigation. 2012; 42 (6):637-648 - 6.
Unal F, Taner G, Yuzbasioglu D, Yilmaz S. Antigenotoxic effect of lipoic acid against mitomycin-C in human lymphocyte cultures. Cytotechnology. 2013; 65 (4):553-565 - 7.
Watanabe M, Kobayashi H, Ohta T. Rapid inactivation of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone (MX), a potent mutagen in chlorinated drinking water, by sulfhydryl compounds. Mutation Research/Environmental Mutagenesis and Related Subjects. 1994; 312 (2):131-138 - 8.
Marnewick JL, Gelderblom WC, Joubert E. An investigation on the antimutagenic properties of south African herbal teas. Mutation Research, Genetic Toxicology and Environmental Mutagenesis. 2000; 471 (1–2):157-166 - 9.
Ozturkcan SA, Turhan K, Turgut Z, Karadayi M, Gulluce M. Antigenotoxic properties of two newly synthesized β-aminoketones against N-methyl-N′-nitro-N-nitrosoguanidine and 9-aminoacridine-induced mutagenesis. Journal of Biochemical and Molecular Toxicology. 2012; 26 (7):258-263 - 10.
Şakiyan İ, Anar M, Öğütcü H, Agar G, Sarı N. Schiff bases attached L-glutamine and L-asparagine: First investigation on antimutagenic and antimicrobial analyses. Artificial cells, Nanomedicine, and Biotechnology. 2014; 42 (3):199-204 - 11.
Kakinuma K, Koike J, Kotani K, Ikekawa N, Kada T, Nomoto M. Cinnamaldehyde: Identification of an antimutagen from a crude drug, cinnamoni cortex. Agricultural and Biological Chemistry. 1984; 48 (7):1905-1906 - 12.
Kakinuma K, Okada Y, Ikekawa N, Kada T, Nomoto M. Antimutagenic diterpenoids from a crude drug isodonis herba (Enmei-so). Agricultural and Biological Chemistry. 1984; 48 (6):1647-1648 - 13.
Clarke CH, Shankel DM. Antimutagenesis in microbial systems. Bacteriological Reviews. 1975; 39 (1):33 - 14.
Zahin M, Ahmad I, Gupta RC, Aqil F. Punicalagin and ellagic acid demonstrate antimutagenic activity and inhibition of benzo [a] pyrene induced DNA adducts. BioMed Research International. 2014; 2014 :1-10 - 15.
Orhan F, Barış Ö, Yanmış D, Bal T, Güvenalp Z, Güllüce M. Isolation of some luteolin derivatives from Mentha longifolia (L.) Hudson subsp. longifolia and determination of their genotoxic potencies. Food Chemistry. 2012;135 (2):764-769 - 16.
Orhan F, Gulluce M, Ozkan H, Alpsoy L. Determination of the antigenotoxic potencies of some luteolin derivatives by using a eukaryotic cell system, Saccharomyces cerevisiae . Food Chemistry. 2013;141 (1):366-372 - 17.
Vilar JB, Ferreira FL, Ferri PH, Guillo LA, Chen Chen L. Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum ( Annona crassiflora Mart. 1841) by micronucleus test in mice. Brazilian Journal of Biology. 2008;68 (1):141-147 - 18.
Okuno Y, Marumoto S, Miyazawa M. Antimutagenic activity of flavonoids from Sozuku. Natural Product Research. 2019; 33 (6):862-865 - 19.
Manon L, Béatrice B, Thierry O, Jocelyne P, Fathi M, Evelyne O, et al. Antimutagenic potential of harpagoside and Harpagophytum procumbens against 1-nitropyrene. Pharmacognosy Magazine. 2015;11 (Suppl 1):S29 - 20.
Rodríguez-Muñoz E, Herrera-Ruiz G, Pedraza-Aboytes G, Loarca-Piña G. Antioxidant capacity and antimutagenic activity of natural oleoresin from greenhouse grown tomatoes ( Lycopersicon esculentum ). Plant Foods for Human Nutrition. 2009;64 (1):46-51 - 21.
Inami K, Mine Y, Tatsuzaki J, Mori C, Mochizuki M. Isolation and characterization of antimutagenic components of Glycyrrhiza aspera against N-methyl-N-nitrosourea. Genes and Environment. 2017;39 (1):5 - 22.
Verma J, Gautam S. Antimutagenic potential of date palm (phoenix dactylifera) fruit aqueous extract in suppressing induced mutagenesis and purification of its bioactive constituent. MOJ Food Process Technol. 2016; 2 (5):179-185 - 23.
Horn RC, Vargas VMF. Antimutagenic activity of extracts of natural substances in the Salmonella /microsome assay. Mutagenesis. 2003;18 (2):113-118 - 24.
Mushtaq M, Sultana B, Anwar F, Batool S. Antimutagenic and antioxidant potential of aqueous and acidified methanol extracts from Citrus limonum fruit residues. Journal of the Chilean Chemical Society. 2015;60 (2):2979-2983 - 25.
Silva VA, Gonçalves GF, Pereira MS, Gomes IF, Freitas AF, Diniz MF, et al. Assessment of mutagenic, antimutagenic and genotoxicity effects of Mimosa tenuiflora . Revista Brasileira de Farmacognosia. 2013;23 (2):329-334 - 26.
Hong C-E, Cho M-C, Jang H-A, Lyu S-Y. Mutagenicity and anti-mutagenicity of Acanthopanax divaricatus var. albeofructus. The Journal of Toxicological Sciences. 2011;36 (5):661-668 - 27.
Del-Toro-Sánchez CL, Bautista-Bautista N, Blasco-Cabal JL, Gonzalez-Ávila M, Gutiérrez-Lomelí M, Arriaga-Alba M. Antimutagenicity of methanolic extracts from Anemopsis californica in relation to their antioxidant activity. Evidence-based Complementary and Alternative Medicine. 2014;2014 :1-8 - 28.
Toscano-Garibay J, Arriaga-Alba M, Sánchez-Navarrete J, Mendoza-García M, Flores-Estrada J, Moreno-Eutimio M, et al. Antimutagenic and antioxidant activity of the essential oils of Citrus sinensis andCitrus latifolia . Scientific Reports. 2017;7 (1):1-9 - 29.
Ruiz-Pérez NJ, Arriaga-Alba M, Sánchez-Navarrete J, Camacho-Carranza R, Hernández-Ojeda S, Espinosa-Aguirre JJ. Mutagenic and antimutagenic effects of Heterotheca inuloides . Scientific Reports. 2014;4 :6743 - 30.
Boubaker J, Mansour HB, Ghedira K, Chekir-Ghedira L. Antimutagenic and free radical scavenger effects of leaf extracts from Accacia salicina . Annals of Clinical Microbiology and Antimicrobials. 2011;10 (1):37 - 31.
Pesarini J, Zaninetti P, Mauro M, Carreira C, Dichi J, Ribeiro L, et al. Antimutagenic and anticarcinogenic effects of wheat bran in vivo. Genetics and Molecular Research. 2013; 12 :1646-1659 - 32.
Satyendra G, Sudhanshu S, Sanjeev K. Fruits and vegetables as dietary sources of antimutagens. Journal of Food Chemistry and Nanotechnology. 2016; 2 (3):97-114 - 33.
Edenharder R, Kurz P, John K, Burgard S, Seeger K. In vitro effect of vegetable and fruit juices on the mutagenicity of 2-amino-3-methylimidazo [4, 5-f] quinoline, 2-amino-3, 4-dimethylimidazo [4, 5-f] quinoline and 2-amino-3, 8-dimethylimidazo [4, 5-f] quinoxaline. Food and Chemical Toxicology. 1994; 32 (5):443-459 - 34.
Saxena S, Verma J, Gautam S. Potential prophylactic properties of apple and characterization of potent bioactive from cv.“granny smith” displaying strong antimutagenicity in models including human lymphoblast TK6+/− cell line. Journal of Food Science. 2016; 81 (2):H508-H518 - 35.
Batista ÂG, Ferrari AS, da Cunha DC, da Silva JK, Cazarin CBB, Correa LC, et al. Polyphenols, antioxidants, and antimutagenic effects of Copaifera langsdorffii fruit. Food Chemistry. 2016;197 :1153-1159 - 36.
Lee H-R, Lim H-B. Antimutagenic and antioxidative effects of polysaccharides isolated from the water extract of Ganoderma lucidum . Journal of Applied Pharmaceutical Science. 2019;9 (04):001-007 - 37.
Ajith T, Janardhanan K. Antimutagenic effect of Phellinus rimosus (Berk) Pilat against chemical induced mutations of histidine dependent Salmonella typhimurium strains. Food and Chemical Toxicology. 2011;49 (10):2676-2680 - 38.
Słoczyńska K, Pańczyk K, Waszkielewicz AM, Marona H, Pękala E. In vitro mutagenic, antimutagenic, and antioxidant activities evaluation and biotransformation of some bioactive 4-substituted 1-(2-methoxyphenyl)piperazine derivatives. Journal of Biochemical and Molecular Toxicology. 2016; 30 (12):593-601 - 39.
Wilpart M, Speder A, Ninane P, Roberfroid M. Antimutagenic effects of natural and synthetic hormonal steroids. Teratogenesis, Carcinogenesis, and Mutagenesis. 1986; 6 (4):265-273 - 40.
Gao C, Chang P, Yang L, Wang Y, Zhu S, Shan H, et al. Neuroprotective effects of hydrogen sulfide on sodium azide-induced oxidative stress in PC12 cells. International Journal of Molecular Medicine. 2018; 41 (1):242-250 - 41.
Shan H, Chu Y, Chang P, Yang L, Wang Y, Zhu S, et al. Neuroprotective effects of hydrogen sulfide on sodium azide-induced autophagic cell death in PC12 cells. Molecular Medicine Reports. 2017; 16 (5):5938-5946 - 42.
Sasaki Y, Matsumoto K, Imanishi H, Watanabe M, Ohta T, Shirasu Y, et al. In vivo anticlastogenic and antimutagenic effects of tannic acid in mice. Mutation Research Letters. 1990; 244 (1):43-47 - 43.
Gulluce M, Agar G, Baris O, Karadayi M, Orhan F, Sahin F. Mutagenic and antimutagenic effects of hexane extract of some Astragalus species grown in the eastern Anatolia region of Turkey. Phytotherapy Research. 2010; 24 (7):1014-1018 - 44.
De Flora S, Izzotti A, D’Agostini F, Balansky RM, Noonan D, Albini A. Multiple points of intervention in the prevention of cancer and other mutation-related diseases. Mutation Research, Fundamental and Molecular Mechanisms of Mutagenesis. 2001; 480 :9-22 - 45.
Koçer S, Uruş S, Çakır A, Güllüce M, Dığrak M, Alan Y, et al. The synthesis, characterization, antimicrobial and antimutagenic activities of hydroxyphenylimino ligands and their metal complexes of usnic acid isolated from Usnea longissima . Dalton Transactions. 2014;43 (16):6148-6164 - 46.
Nartop D, Demirel B, Güleç M, Hasanoğlu Özkan E, Kurnaz Yetim N, Sarı N, et al. Novel polymeric microspheres: Synthesis, enzyme immobilization, antimutagenic activity, and antimicrobial evaluation against pathogenic microorganisms. Journal of Biochemical and Molecular Toxicology. 2019; 34 :e22432 - 47.
Alexandrova V, Obukhova G, Topchiev D. Synthesis and antimutagenic properties of novel systems based on poly (quaternized ammonium) salts. Journal of Bioactive and Compatible Polymers. 2002; 17 (5):321-341 - 48.
Giziroglua E, Sarikurkcub C, Saracc N. Synthesis and characterization of novel Hydrazone based anti-mutagenic and Antioxidative agents. Journal of Applied Pharmaceutical Science. 2015; 5 (3):048-055 - 49.
De Oliveira APS, De Sousa JF, Da Silva MA, Hilário F, Resende FA, De Camargo MS, et al. Estrogenic and chemopreventive activities of xanthones and flavones of Syngonanthus (Eriocaulaceae). Steroids. 2013;78 (11):1053-1063 - 50.
Nartop D, Özkan EH, Gündem M, Çeker S, Ağar G, Öğütcü H, et al. Synthesis, antimicrobial and antimutagenic effects of novel polymeric-Schiff bases including indol. Journal of Molecular Structure. 2019; 1195 :877-882 - 51.
Olejníková P, Birošová L, Lu Š, Vihonská Z, Fiedlerová M, Marchalín Š, et al. Newly synthesized indolizine derivatives—Antimicrobial and antimutagenic properties. Chemical Papers. 2015; 69 (7):983-992 - 52.
Roy SS, Chakraborty P, Ghosh P, Ghosh S, Biswas J, Bhattacharya S. Influence of novel naphthalimide-based organoselenium on genotoxicity induced by an alkylating agent: The role of reactive oxygen species and selenoenzymes. Redox Report. 2012; 17 (4):157-166 - 53.
Zhang J, Tian Q, Yung Chan S, Chuen Li S, Zhou S, Duan W, et al. Metabolism and transport of oxazaphosphorines and the clinical implications. Drug Metabolism Reviews. 2005; 37 (4):611-703 - 54.
El-Sayed WM, Hussin WA, Al-Faiyz YS, Ismail MA. The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo [1, 2-a] pyridine derivatives. European Journal of Pharmacology. 2013; 715 (1–3):212-218 - 55.
Collins AR, Azqueta A, Langie SA. Effects of micronutrients on DNA repair. European Journal of Nutrition. 2012; 51 (3):261-279 - 56.
Kumar SS, Negi P, Manjunatha J, Bettadaiah B. Synthesis, antibacterial and antimutagenic activity of zerumbone-bicarbonyl analogues. Food Chemistry. 2017; 221 :576-581 - 57.
Leonova E, Rostoka E, Sauvaigo S, Baumane L, Selga T, Sjakste N. Study of interaction of antimutagenic 1, 4-dihydropyridine AV-153-Na with DNA-damaging molecules and its impact on DNA repair activity. PeerJ. 2018; 6 :e4609 - 58.
Maslat A, Khalil A, Fares A, Tashtoush H, El-Talib M. A notable antimutagenicity of two nonmutagenic novel oxadiazoles in Salmonella mutagenicity assay. Drug and Chemical Toxicology. 2005;27 (2):157-167 - 59.
Ashram M, Maslat A, Mizyed S. Synthesis and biological activities of new azacrown ether Schiff bases and spectrophotometric studies of their complexation with [60] fullerene. Toxicological and Environmental Chemistry. 2009; 91 (6):1095-1104