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Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Furthermore, a thorough alkylation analysis was performed on the phage R17 with two groups of alkylating agents: (i) methyl methanesulfonate and dimethyl sulfate and (ii) N-methyl-N-nitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine (Shooter 1974b). The extent of biological inactivation by these alkylating agents was explained by the breaks in the RNA chain, which resulted from hydrolysis of phosphotriesters formed in the alkylation reactions and the rate of hydrolysis increased rapidly as the pH was raised (Shooter et al. 1974a). The mechanism of the biological inactivation of the phage R17 by ethyl methanesulfonate and N-ethyl-N-nitrosourea was unveiled (Shooter and Howse 1975). Then, a group of eight alkylating agents was involved in the R17 studies (Shooter 1975) and acetoxy-dimethylnitrosamine was tested (Shooter and Wiessler 1976).
Chemical and Functional Properties of Amazonian Fruits
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Elaine Pessoa, Josilene Lima Serra, Hervé Rogez, Sylvain Darnet
Oyeyemi et al. (2015) demonstrated that doses of 5000 mg kg−1per os aqueous and hydroethanolic extracts of yellow mombin leaf did not induce acute toxicity in mice. In contrast, hydromethanolic extracts showed genotoxicity and antigenotoxicity action. The results of the genotoxicity tests in mice revealed genotoxic effects of hydromethanolic extracts with the potential to induce both somatic and germline genetic damage. The extracts also showed antigenotoxicity action and reduced genotoxicity induced by methyl methanesulfonate in bone marrow cells of the exposed mice. Therefore, studies suggested the therapeutic effects of yellow mombin leaf extract and that consumption for a long time should have toxic effects (Oyeyemi et al., 2015).
DNA — The Critical Cellular Target in Chemical Carcinogenesis?
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
The high degree of correlation between mutagenesis and carcinogenesis by chemicals might well be circumstantial and cannot prove a causal relationship between these two biological processes. Both processes, however, apparently require the initiating action of highly reactive chemicals. Indeed, the relatively high yields of transformants (over 10%; see Table 8) sometimes obtained with chemical carcinogens133-135 when compared to the very low frequencies of induced mutation in mammalian cell cultures (10−6 per gene per cell division)136 speak strongly against conventional random mutations as the basis of chemical carcinogenesis. In an effort to overcome one argument against such comparisons, namely, that these two biological effects were studied in different cells (see above), we are currently attempting to determine the mutation rates resulting from treatment with chemicals in our cloned, transformable M2 mouse cell line. In accordance with the results in Table 8, our preliminary results also indicate that malignant transformation is an event that is much more frequent than mutagenesis (Table 9). It should be noted, however, that with mouse myeloma cells in which the spontaneous mutation frequency (to variants producing an altered immunoglobulin) is unusually high (10−3 per cell generation), treatment with chemical mutagens results in the induction of an even higher yield of variants that are probably mutants.137 As far as the high transformation frequency is concerned, the results of some experiments by Di-Paolo and co-workers167 argue against the somatic mutation theory. They found that, while pretreatment of Syrian hamster embryo cells with the alkylating agent methyl methanesulfonate did enhance malignant transformation by N-acetoxy-2-acetylaminofluorene, such pretreatment did not affect mutagenesis induced in V79 Chinese hamster cells with N-acetoxy-2-acetylaminofluorene.
Genomic DNA damage induced by co-exposure to DNA damaging agents and pulsed magnetic field
Published in International Journal of Radiation Biology, 2023
Beatriz López-Díaz, Silvia Mercado-Sáenz, Antonio M. Burgos-Molina, Alejandro González-Vidal, Francisco Sendra-Portero, Miguel J. Ruiz-Gómez
In this work, we have used bleomycin (Figure 1(a)) and methyl methanesulfonate (MMS) (Figure 1(b)) as genotoxic agents in co-exposure to pulsed MF. Bleomycin is an antineoplastic agent that belongs to the group of antitumoral antibiotics used in the treatment of squamous cell carcinoma, Hodgkin disease and non-Hodgkin lymphoma, among others. It is a radiomimetic agent whose mechanism of action consists in the generation of ROS which react with the DNA molecules causing their fragmentation (Obe et al. 2010). MMS is a genotoxic alkylating agent that exhibits activity on the nitrogenous rings of puric bases, producing the methylation of adenine and guanine bases. It is used as a model drug, causing poorly paired bases that lead to DNA fragmentation. It could be also considered a radiomimetic agent (Lundin et al. 2005; Ovejero et al. 2021).
Antioxidant and in vitro cytogenotoxic properties of Amburana cearensis (Allemão) A.C.Sm. leaf extract
Published in Drug and Chemical Toxicology, 2023
José Rafael da Silva Araujo, Juliana Vieira de Barros Arcoverde, Marília Grasielly de Farias Silva, Edson Renan Barros de Santana, Persio Alexandre da Silva, Silvany de Sousa, Neide Santos, Pedro Marcos de Almeida, Cláudia Sampaio de Andrade Lima, Ana Maria Benko-Iseppon, Rafael Jorge Santos Aracati Padilha, Marccus Alves, Ana Christina Brasileiro-Vidal
The CBMN test was performed to assess the safety of the most active antioxidant fraction (EtOAc), following Fenech (2007) with some modifications. Peripheral venous blood (0.5 mL) from three donors was incubated into tubes containing 5 mL of RPMI 1640 with 10% fetal bovine serum and 10% streptomycin, and 0.1 mL phytohemagglutinin for each treatment. After 20 h stabilization, the cells were exposed to the samples with 100, 200, and 400 µg/mL concentrations; 2 × 10−2 M methyl methanesulfonate (MMS; PC); only medium (NC), and 0.006% ethanol (SC). The concentrations were selected based on the MTT test (100, 200, and 400 µg/mL). The last two concentrations were selected based on the ICH guideline S2 (R1) from the European Medicines Agency and Food and Drug Administration (European Medicines Agency (EMA) 2013, Food and Drug Administration (FDA) 2012), which recommends concentrations with no cytotoxicity or less than 50% of reduction for in vitro cytogenotoxic assays.
Short-term oral administration of non-porous and mesoporous silica did not induce local or systemic toxicity in mice
Published in Nanotoxicology, 2020
Joan Cabellos, Irene Gimeno-Benito, Julia Catalán, Hanna K. Lindberg, Gerard Vales, Elisabet Fernandez-Rosas, Radu Ghemis, Keld A. Jensen, Rambabu Atluri, Socorro Vázquez-Campos, Gemma Janer
Groups of eight mice per treatment and dose level were administered by oral gavage once a day during a period of five consecutive days. The control group was administered the vehicle (CMC-Tween80®) that was used to prepare the particle suspensions. The administration volume was 10 mL/kg body weight (b.w.). Particle dispersions were prepared at 10 mg/mL and 100 mg/mL as described above to obtain 100 mg/kg b.w. (Low dose; LD) and 1000 mg/kg b.w. (high dose; HD), respectively. Two follow-up periods were selected after the last administration: 24-h (day 6 of the experiment) or 21 days (day 26 of the experiment; Recovery group). Two additional groups of 8 animals each were orally administered with Methyl methanesulfonate (MMS, Sigma-Aldrich, St. Louis, MO, USA), a DNA alkylating agent used as a positive control for genotoxicity (Comet assay in the intestine). MMS was administered at 100 mg/kg b.w. during 3 consecutive days, at 48 h, 24 h, and 2–3 h prior to each termination date.