Evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young rats

Suzuki, Hiroshi; Ikeda, Naohiro; Kobayashi, Kazuo; Terashima, Yukari; Shimada, Yasushi; Suzuki, Takayoshi; Toshiyuki, Hagiwara; Hatakeyama, Shigeki; Nagaoka, Koko; Yoshida, Junichi; Saito, Yukiko; Tanaka, Jin; Hayashi, Makoto

doi:10.1016/j.mrgentox.2005.03.012

Cited by 72 publications

(46 citation statements)

References 37 publications

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“…not to induce MN in young rats (4 weeks old). However, KA induced MN in peripheral blood of young rats (6). At present, neither the molecular mechanism of the genotoxicity of KA, nor the diŠer-ence in metabolisms between rats and mice is known.…”

Section: Discussionmentioning

confidence: 97%

“…KA which had been used as a food additive for the prevention of enzymatic browning of shellˆsh, raw crabs and shrimp, owing to its inhibitory activity on tyrosinase, was found to be genotoxic in vitro, inducing his ＋ reverse mutations in S. typhimurium (2-5). It was also found to be genotoxic in vivo, inducing micronuclei (MN) in peripheral blood of rats (6). KA had been reported to induce hepatomas and thyroid adenomas in mice (7).…”

Section: Introductionmentioning

confidence: 99%

“…Many contradictory or inconsistent results had been reported for the genotoxicity of KA. KA induced MN in peripheral blood, but not in the liver of young rats by a single application through gastric intubation (6). However, it did not induce MN in bone marrow of mice (12,13) Since there had been no standards for composition of KA in food hygiene law, while the manufacturers' speciˆcations for cosmetic use was at least 97z pure, there was a possibility that the discordance reported for genotoxicity was due to diŠerences in composition of KA samples used.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver

Ishikawa

Sasaki

Kawaguchi

et al. 2006

Genes and Environment

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Three lots of kojic acid (KA) which were produced for use as a reagent, food additive and in cosmetics were shown to be mutagenic in S. typhimurium TA100 with or without S9 mix, with a speciˆc activity of around 100 revertants per mg of KA. Since there are contradictory reports on genotoxicity of KA, we examined, using HPLC, whether the mutagenicity to S. typhimurium is due to KA itself, or due to contaminants present in the KA samples. Although two UV absorbing fractions were separated by HPLC, mutagenicity was detected only in the major fraction and the speciˆc mutagenic activity of KA did not change before and after HPLC separation. The material in the major peak fractions on HPLC was conˆrmed to be KA by NMR. Thus it was demonstrated that KA itself is mutagenic and no mutagenic contaminants were detected in the three lots of samples. Since KA is known to produce liver tumors in mice, we further examined the genotoxicity of KA in the liver of rodents. KA induced micronuclei (MN) in the regenerating liver of adult mice by its gastric intubation at 1 g per kg body weight. However, no MN were induced in young mice (3 weeks old) without partial hepatectomy. Since it was recently found that KA had no tumor-initiating activity in the liver of mice in a two-step carcinogenicity study, there is no evidence that the genotoxicity detected in the mouse liver is involved in liver carcinogenesis.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver

Ishikawa

Sasaki

Kawaguchi

et al. 2006

Genes and Environment

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“…Furthermore, in vivo carcinogenicity tests have identified MDA as a potent hepatic carcinogen (16). In contrast, MDA was found to be negative to weakly positive for genotoxicity in hematopoietic cells and the liver by in vivo genotoxicity tests, such as the micronucleus and unscheduled DNA synthesis tests (17)(18)(19). Therefore, we examined the mutagenic properties of MDA in the peripheral blood of rats during 1-and 28-day dosing using Pig-a gene mutation assays, including the RBC Pig-a and PIGRET assays, and confirmed the utility of these assays.…”

Section: Introductionmentioning

confidence: 89%

“…In this study, gene mutations were observed at higher dose than that observed hepatic carcinoma using rats in carcinogenicity test (16), which suggests the difference in an exposure between target and un-target tissues. In addition, this assay detected the genotoxicity of MDA judged to be negative in hematopoietic cell in micronucleus test (17,18), so the cumulative effect was thought to be useful in the detection of weakly mutagenic compounds. However, the toxicities related to the erythrocytes reduction and metabolic alteration are thought to influence the sensitivity, it is necessary to select the dose and sampling time suitable for each compound.…”

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confidence: 99%

Evaluation for a Mutagenicity of 4,4^|^prime;-Methylenedianiline on Hematopoietic Cells by a Pig-a Gene Mutation Assay in Rats

Sanada

Okamoto

Ohsumi

et al. 2014

Genes and Environment

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The Pig-a gene is involved in the synthesis of glycosylphosphatidylinositol (GPI) anchors. Pig-a gene mutations can be detected by identifying the presence of CD59, the GPI anchor protein, on the surface of erythrocytes (RBC Pig-a assay) and reticulocytes (PIGRET assay) and can be identified using flow cytometry. The usefulness of these Pig-a gene mutation assays has been confirmed in multilaboratory trials with referenced mutagens. Although 4, 4′ -methylenedianiline (MDA) is an aromatic amine and has been identified as a potent hepatic carcinogen, in vivo micronucleus tests for MDA in hematopoietic cells determined that it was negative to weakly positive for genotoxicity. In the present study, we examined the mutagenicity of MDA in the peripheral blood of rats after 1-and 28-day MDA dosing using the Pig-a gene mutation assays. We also examined the utility of the RBC Pig-a and PIGRET assays. No changes in mutation frequency were observed after one-day MDA administration. Repeated dosing caused a moderate increase in mutation frequency compared to vehicle control at days 14 and 28, as measured by the RBC Pig-a assay and at day 14 by the PIGRET assay. The highest mutation frequency was found on days 7 and 14 by the PIGRET and RBC Pig-a assays, respectively.In this study, we detected the mutagenicity of MDA in peripheral blood samples using gene mutation assays and judged to be positive for the MDA mutagenicity since a significant increase in mutation frequency was observed at high dose. These assays are expected to be easily integrated into general toxicity tests and to be combined with existing genotoxicity studies.

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Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

Darby

2023

Patty's Toxicology

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The fundamental aromatic hydrocarbon benzene, when substituted by one or more functional groups of the amine, nitro, or halogen classes, alone or in various combinations, provides an enormous number of compounds of immense practical value, ubiquitous presence in the industrial world, and often heightened toxicity relative to benzene itself, a notorious cause of blood cancer. This chapter begins by providing a general overview of aromatic compounds possessing amino and/or nitro substituents, with or without halogen substituents. The production and uses, exposure and biomonitoring, toxicity, and toxic mechanism of action are introduced. The remainder of the chapter focuses on specific compounds in a roughly systematic order based upon chemical structure, expanding on the same subheadings as covered in the general overview. The nomenclature of these compounds can be very confusing since many have traditional names that sometimes markedly differ from their systematized formal names. In this chapter, the same traditional names are used as were used in the previous edition of this publication, but if there is ambiguity of nomenclature, the Chemical Abstracts Service (CAS) numbers provided herein correspond to unique structures, each of which may have several names depending upon the naming convention. In general, when an aromatic compound has an amino or a nitro substituent, it is referred to as an “aniline” or a “nitrobenzene,” respectively, based upon the names of the parent compounds, even though other substituents may be present. When amino and nitro groups are present on the same benzene ring, “aniline” takes precedence, and both “aniline” and “nitrobenzene” take precedence over halogens. There are many exceptions to these general rules, however.

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Evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young rats

Cited by 72 publications

References 37 publications

Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver

Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver

Evaluation for a Mutagenicity of 4,4^|^prime;-Methylenedianiline on Hematopoietic Cells by a Pig-a Gene Mutation Assay in Rats

Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

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