Aberrant cell cycle regulation in rat liver cells induced by post-initiation treatment with hepatocarcinogens/hepatocarcinogenic tumor promoters

Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

doi:10.1016/j.etp.2016.06.002

Cited by 3 publications

(5 citation statements)

References 28 publications

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“…Some studies have mentioned that CBX causes abnormal cell cycle regulation and is closely associated with hereditary liver carcinogens. 21 It was also reported that the addition of trace amounts of CBX could increase the incidence of diarrhea and systemic inflammation caused by E. coli infection in weaned piglets. 23 Specially, CBX may contribute to the emergence of strains carrying phage-encoded resistance determinants clusters in combination with other antibiotics in growing livestock.…”

Section: ■ Introductionmentioning

confidence: 97%

“…Toxicity investigations about CBX exhibit genetic reproductive toxicity, carcinogenicity, teratogenicity, and mutagenic toxicity. 21 CBX was mentioned as a specific antimicrobial agent with a 97.9% likelihood of causing cancer in humans. 22 Carcinogenicity is one of the most severe toxic effects of CBX.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Carcinogenicity is one of the most severe toxic effects of CBX. Some studies have mentioned that CBX causes abnormal cell cycle regulation and is closely associated with hereditary liver carcinogens . It was also reported that the addition of trace amounts of CBX could increase the incidence of diarrhea and systemic inflammation caused by E.…”

Section: Introductionmentioning

confidence: 99%

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Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

An,

Li,

et al. 2024

Chem. Res. Toxicol.

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Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.

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Section: ■ Introductionmentioning

confidence: 97%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

An,

Li,

et al. 2024

Chem. Res. Toxicol.

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“…Recently, due to the high-antimicrobial activity, QdNOs are also used in aquaculture, especially in holothurian culture [ 3 ]. However, recently literatures showed that the toxicity of QdNOs is high, which might induce potential carcinogenicity and mutagenicity [ 4 – 6 ]. It was also reported that MEQ might also induce liver and adrenal toxicity at high or low dose after oral administration [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…MEQ was also reported to cause methylation of holothurian DNA, which was one of the expression forms of DNA damage [ 9 , 10 ]. Now, as members of QdNOs, carbadox and olaquindox (CBX and OLA) have been banned as the feed additives in the past decades [ 4 – 6 ]. Therefore, MEQ and its metabolites residues should be paid close attention.…”

Section: Introductionmentioning

confidence: 99%

UPLC-MS/MS Method for Simultaneous Determination of Three Major Metabolites of Mequindox in Holothurian

Liu

Ren

Han

et al. 2018

Journal of Analytical Methods in Chemistry

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This study developed an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the detection of three major metabolites of mequindox, including 3-methyl-quinoxaline-2-carboxylic acid, 1-desoxymequindox, and 1,4-bisdesoxymequindox (MQCA, 1-DMEQ, and BDMEQ), in holothurian. Target analytes were simplified with ultrasound-assisted acidolysis extracted without complicated enzymolysis steps. After that, each sample was centrifuged and purified by an Oasis MAX cartridge. Then, the processed samples were separated and monitored by UPLC-MS/MS. This developed method has been validated according to FDA criteria. At fortified levels of 2, 10, and 20 μg/kg, recoveries ranged from 82.5% to 93.5% with the intraday RSD less than 7.27% and interday RSD less than 11.8%. The limit of detection (LOD) of all the three metabolites ranged from 0.21 to 0.48 μg/kg, while the limit of quantification (LOQ) ranged from 0.79 to 1.59 μg/kg. On application to commercial samples, 14 of 20 samples were detected positive for the three target analytes, with positive rate at 70 percentage. The result indicated that this method was specific, sensitive, and suitable for the quantification and conformation of the three major metabolites of MEQ in holothurian.

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A Convenient and Sensitive LC-MS/MS Method for Simultaneous Determination of Carbadox- and Olaquindox-Related Residues in Swine Muscle and Liver Tissues

Zhang

Tao

et al. 2018

Journal of Analytical Methods in Chemistry

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This paper presents a convenient and sensitive LC-MS/MS method for the simultaneous determination of carbadox and olaquindox residues, including desoxyolaquindox (DOLQ), desoxycarbadox (DCBX), quinoxaline-2-carboxylic acid (QCA), 3-methyl-quinoxaline-2-carboxylic acid (MQCA), and the glycine conjugates of QCA and MQCA (namely, QCA-glycine and MQCA-glycine, resp.) in swine muscle and liver tissues. Tissue samples were extracted with 2% metaphosphoric acid in 20% methanol and cleaned up by solid-phase extraction (SPE) on a mixed-mode anion-exchange column (Oasis MAX). Analysis was performed on a C18 column by detection with mass spectrometry in the multiple reaction monitoring (MRM) mode. The limits of detection (LODs) of the six analytes were determined to be 0.01 μg·kg−1 to 0.25 μg·kg−1, and the limits of quantification (LOQs) were 0.02 μg·kg−1 to 0.5 μg·kg−1. The total recoveries of the six analytes in all tissues were higher than 79.1% with the RSD% less than 9.2%. The developed method can determine the real residue level of QCA and MQCA, whether they are present in free form or as glycine conjugates in tissues, together with the carcinogenic desoxy metabolites DCBX and DOLQ with high recovery. Therefore, this method was suitable for routine analysis of residue control programmes and the residue depletion study of CBX and OLQ on swine.

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Aberrant cell cycle regulation in rat liver cells induced by post-initiation treatment with hepatocarcinogens/hepatocarcinogenic tumor promoters

Cited by 3 publications

References 28 publications

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

UPLC-MS/MS Method for Simultaneous Determination of Three Major Metabolites of Mequindox in Holothurian

A Convenient and Sensitive LC-MS/MS Method for Simultaneous Determination of Carbadox- and Olaquindox-Related Residues in Swine Muscle and Liver Tissues

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