Fenugreek in Management of Female-Specific Health Conditions
Dilip Ghosh, Prasad Thakurdesai in Fenugreek, 2022
For regulatory purposes, a chemical’s mutagenicity potential has mainly been evaluated using in vitro assays, such as the Bacterial Reverse Mutation Test, AMES test (Mortelmans and Zeiger 2000). Mutagens are agents that can cause heritable changes in DNA, and their capacity to cause mutations is defined as mutagenicity (Cvetković, Takić Miladinov, and Stojanović 2018). As all information for the proper development, functioning, and reproduction of organisms is coded in DNA, mutations can result in harmful effects and play a role in genetic disorders (Verheyen 2017), especially for food-related products (Mandal et al. 2018; Weisburger 1999). The structural chromosomal abnormalities such as chromosomal aberration (a missing, extra, or irregular portion of chromosomal DNA) result from breakage and incorrect rejoining of chromosomal segments and result in many genetic diseases disorders such as cancer (Nguyen 2020). The standardized fenugreek seed extracts with markers such as furostenol saponins, glycosides, or low molecular galactomannans such as FENU-FG, SFSE-G, and LMWGAL-TF, were found safe and devoid of mutagenicity (OECD Test No. 471) and genotoxicity (Mammalian Chromosomal Aberration, OECD Test No. 473) potential during these studies (Deshpande, Mohan, and Thakurdesai 2016a; Deshpande, Mohan, Ingavale et al. 2017).
Experimental Colon Carcinogens and Their Mode of Action
Herman Autrup, Gary M. Williams in Experimental Colon Carcinogenesis, 2019
This sequence of metabolic oxidations of DMH yielding the reactive eletrophile was believed to be responsible for the genotoxic effects of the carcinogen through the al-kylation of colon, liver, and kidney DNA as observed in vivo and in vitro, and through the demonstration of the formation of mutagenic products. 1,9,31,71–88 Early workers had difficulty demonstrating the mutagenicity of DMH in the Ames Salmonella typhimu-rium test system. However, once the specific metabolic sequence was elucidated and the proper experimental conditions elaborated, mutagenicity was observed both in host-mediated assays and in vitro.79,80,84 With the chemically related procarbazine (Na- tulan), mutagenicity in the Ames test was still unreliable,89 even though this compound is carcinogenic, although not to the colon.
Metabolic Activation of Aromatic Amines and Amides and Interactions with Nucleic Acids
Philip L. Grover in Chemical Carcinogens and DNA, 2019
In addition to the formation of covalent bonds between aromatic amines and amides and DNA, there are some indications that physical interaction can occur between these carcinogens, or their metabolites, and DNA. This possibility cannot be excluded and this type of interaction may play a role in carcinogenesis. Mutagenicity tests by Ames et al.129 suggest that the combination of intercalation and covalent binding causes a strong mutagenic effect as, for example, in the case of 2-nitrosofluorene. This compound appeared to be an effective frame-shift mutagen. However, more recent findings do not support the intercalation hypothesis. The mutagenicity exhibited by 2-nitrosofluorene could be caused by the ability of the Salmonella typhimurium strain to reduce the compound to N-hydroxy-AF, since nitroreductase has been shown to be present in this group of bacteria by Fukuda and Yamamoto130 and since Durston and Ames131 showed that N-hydroxy-AF is a strong mutagen in their test system. These findings are supported by the results of Stout et al.,132 who demonstrated that, upon incubation of N-hydroxy-AAF with liver cytosol, N-hydroxy-AF is the major mutagenic metabolite formed. An additional difficulty in the interpretation of the results from Durston and Ames131 is the fact that on incubation of N-hydroxy-AF, the compound is rapidly transformed to 2-nitrosofluorene and 2,2′-azoxyfluorene.
Exploring graphene-based materials’ genotoxicity: inputs of a screening method
Published in Nanotoxicology, 2021
Salma Achawi, Ludovic Huot, Fabrice Nesslany, Jérémie Pourchez, Sophie Simar, Valérie Forest, Bruno Feneon
Briefly, aneugenicity, clastogenicity or mutagenicity are major genotoxicity mechanisms. For aneugenicity, genotoxicants act primarily on non-DNA targets (microtubule, centrosome or kinetochore (More et al. 2021)) or cause damage to the mitosis apparatus, leading to improper chromosome segregation (Parry et al. 1996, 2002). For clastogenicity, structural chromosome aberrations such as chromatid/chromosome breaks occur (Bignold 2009). Clastogenic agents can covalently bind to DNA or enzymes, leading to chromosome breakage. Mutagenicity corresponds to the induction of DNA mutations (Kumar et al. 2018), either by direct interaction with DNA or chromatin or by indirect mechanisms, such as through generation of reactive oxygen species or inflammation (DeMarini 2019). Genotoxicity is associated to serious health effects, the first one being cancer (Phillips and Arlt 2009): some genotoxic agents can indeed cause mutations that can eventually lead to malign tumor. Hence, most carcinogenic chemicals are genotoxic (Hayashi 1992), which make the measurement of this endpoint critical for hazard assessment.
5-Hydroxymethylfurfural (HMF) formation, occurrence and potential health concerns: recent developments
Published in Toxin Reviews, 2021
Ankit Choudhary, Vikas Kumar, Satish Kumar, Ishrat Majid, Poonam Aggarwal, Sheenam Suri
Mutagen is an agent that alters the genetic material of an organism resulting in a mutation. Different studies demonstrate that HMF act as an indirect mutagen toward different strains of organisms. Glatt et al. (2005) showed that HMF and metabolites of HMF i.e. 2,5-bishydroxymethylfuran exhibited mutagenic activity toward Salmonella typhimurium TA100 which expressed human genome SULT1C2 except for other parental strains. This is due to the reason that HMF is transformed into an active compound, SMF (5-sulfo-oxymethyl ester) by the action of enzyme sulfotransferases. A study also depicted that HMF and other furan derivatives, DMF (2,5-dimethylfuran) showed genotoxic effect in the kidney and colon of mice expressing hSULT1A1/1A2 (HÖie et al.2015). DMF was also found to show genotoxic effect for hematopoietic cells in bone marrow of rats when were allowed to react with DMF (0.1 mM) for 1 h (Fromowitz et al.2012). Also, a study concluded that irrespective of the enzymatic activity, HMF damages the DNA. In V79 derived cell line, 5-HMF resulted in some chromosomal alterations in Chinese hamster (Glatt et al.2005).
Induction of novel inflorescence traits in Chrysanthemum through 60Co gamma irradiation
Published in International Journal of Radiation Biology, 2020
Mohit Kumar Setia, Madhu Bala, Simrat Singh
In this study, both Chrysanthemum cultivars were subjected to radio-sensitivity tests to ascertain and standardize the most effective lethal dose (∼>LD50) of γ-rays for likely induction of novel variants and evolution of mutants in Chrysanthemum under in vivo conditions. In this investigation, irradiation dose at 20 Gy for Thiching Queen with 48% plant survival and in cv. Purnima, 15 Gy dose with percent plant survival of 49% were determined to be optimum LD50. Survival rate of plants decreased linearly with corresponding increase in dose of γ-rays (Figure 1). The highest rate of plant survival (88%) was observed in control, followed by γ-irradiation doses of 5 Gy (85%) and 10 Gy (76%). The least survival rate of irradiated plants (42%) was recorded in plants exposed at γ-ray dose of 20 Gy. Among the two genotypes subjected to radiation mutagenesis, the survival percentage (77.80%) was observed in cv. Thiching Queen which was comparatively higher than with 61.80% survival in cv. Purnima. The interaction between mutagen treatments and varieties was found significant. The non-irradiated (control) plants showed the highest plant survival (94%) followed by radiation exposure at 5 Gy dose with 92% survival in cv. Thiching Queen and the least plant survival (36%) was observed with 20 Gy of radiation dosage in cv. Purnima.
Related Knowledge Centers
- DNA
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- Genetic Recombination
- Chromosome