This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction.
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http://dx.doi.org/10.1016/j.toxlet.2013.11.012 | DOI Listing |
Arch Toxicol
December 2024
Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016, Lisbon, Portugal.
Emerging cellulose nanomaterials (CNMs) may have commercial impacts in multiple sectors, being their application particularly explored in the food sector. Thus, their potential adverse effects in the gastrointestinal tract should be evaluated before marketing. This work aimed to assess the safety of two CNMs (CNF-TEMPO and CMF-ENZ) through the investigation of their cytotoxicity, genotoxicity (comet and micronucleus assays), and capacity to induce reactive oxygen species in human intestinal cells, and their mutagenic effect using the Hprt gene mutation assay.
View Article and Find Full Text PDFGenes Environ
December 2024
Yakult Central Institute, Yakult Honsha Co., Ltd., 5-11 Izumi, Kunitachi-Shi, Tokyo, 186-8650, Japan.
Background: When assessing the genotoxicity of substances containing probiotic candidates, such as lactic acid-producing bacteria, using the in vitro micronucleus test (MNT), bacterial growth in the test medium may reduce the pH of the medium. The low medium pH is known to induce cytotoxicity and false-positive results. In the TK6 cell system, it is difficult to completely remove the bacteria from the medium by washing post-treatment, leading to bacterial growth during the recovery period in the short-term treatment.
View Article and Find Full Text PDFToxicol Res (Camb)
December 2024
Department of Biology, Federal University of Technology, Akure, P.M.B. 704, Akure, 340252, Ondo State, Nigeria.
As the demand for fish increases, the amount of wastewater generated from fishponds is also increasing with potential environmental and public health effects from their indiscriminate disposal. This study aimed at comparative analyses of the physicochemical and heavy metal constituents and potential DNA damage by wastewaters from natural and artificial fishponds using assay. were grown on 3.
View Article and Find Full Text PDFGenes Environ
November 2024
Scientific Product Assessment Center, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-Ku, Yokohama, Kanagawa, 227-8512, Japan.
Background: The rose ketone β-damascone (β-Dam) elicits positive results in the in vitro micronucleus (MN) assay using human lymphocytes, but shows negative outcomes in the Ames test and combined in vivo MN and comet assays. This has led to the interpretation that the in vitro MN result is a misleading positive result. Oxidative stress has been suggested as an indirect mode of action (MoA) for in vitro MN formation, with the α, β-unsaturated carbonyl moiety of the β-Dam chemical structure expected to cause misleading positive results through this MoA.
View Article and Find Full Text PDFAddict Biol
November 2024
University of Western Australia, Crawley, Western Australia, Australia.
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