Detection of micronucleated cells and gene expression changes in glandular stomach of mice treated with stomach-targeted carcinogens

Okada, Emiko; Fujiishi, Yohei; Yasutake, Nobuyoshi; Ohyama, Wakako

doi:10.1016/j.mrgentox.2008.08.018

Cited by 19 publications

(6 citation statements)

References 19 publications

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“…[25] Several studies have shown that NMU is genetoxic “ in vitro ” and “ in vivo ” through induction of sister chromatid exchange, micronuclei, structural chromosomal aberration, aneuploidy and comet assay. [25–29] Our results confirmed the genotoxicity of NMU by showing an increase in the incidence of CAs, MNPCE and DNA fragmentation over the vehicle control group. In fact, NMU has a half life of <1 h under physiological conditions and its genotoxic effect occurs within a very short period of its mechanism.…”

Section: Discussionsupporting

confidence: 78%

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In vivo comparative studies on antigenotoxicity of date palm (Phoenix dactylifera l.) pits extract against DNA damage induced by N-Nitroso-N-methylurea in mice

Diab

Aboul-Ela

2012

Toxicol Int

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Aqueous extract of the date palm (Phoenix dactylifera L.) pits was prepared and its antigenotoxic activity was evaluated against N-Nitroso-N-methylurea (NMU) induced mutagenic effect in mice, using chromosome aberration (CA), micronuclei (MN) and DNA fragmentation assays as experimental end points in male mice. Date pits extract (DPE) was given orally to mice at the dose 25 mg/25 g mouse for successive five days in a week up to four consecutive weeks. NMU was used as mutagen and was given intraperitoneal (i.p) injection at single dose 80 mg/kg b.w., 24 hr after last dose of DPE in pre-treatment regimen and 24 hr before the first dose of DPE in the post-treatment regimen. Mice were scarified after one, two and seven days after the end of treatment. The results have shown that pre-and post-treatment regimens of DPE were significantly restored the DNA damage induced by NMU, as revealed by lowering of the occurrence of CAs and MN in bone marrow cells and inhibition of hepatic DNA fragmentation. These findings suggested that DPE produced their inhibitory activity either by desmutagenic or bioantimutagenic manner in pre-and post-treatment regimens respectively.

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Section: Discussionsupporting

confidence: 78%

“…These activities are largely documented in previous reports. [252629] On the other hand, DPE have proven an efficacy in reduction of number of micronuclei induced by NMU. This reduction is marker of enhanced DNA repair in the cells or due to cell death or apoptosis of heavy DNA damage.…”

Section: Discussionmentioning

confidence: 99%

In vivo comparative studies on antigenotoxicity of date palm (Phoenix dactylifera l.) pits extract against DNA damage induced by N-Nitroso-N-methylurea in mice

Diab

Aboul-Ela

2012

Toxicol Int

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“…These findings referred that MUN can methylate DNA at the O6-position of guanine, causing GC→AT mutations, DNA double-strand breaks, interstrand cross-links, nonrepaired N-methylpurines, and abasic sites [31][32][33][34]. Similarly, MNU produces CAs, MNPCE, and comet tail formation in rodent bone marrow cells, liver, glandular stomach, and peripheral blood lymphocytes of rodents [16,[35][36][37][38]. Surprisingly, the absence of genotoxicity was observed in mouse spermatocytes treated with MNU (80 mg/kg) under experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the cytotoxic, anticancer, and genotoxic activities of Acacia nilotica flowers and their effects on N-methyl-N-nitrosourea-induced genotoxicity in mice

et al. 2022

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Purpose In this study, two main research objectives were examined: (1) the cytotoxic and anticancer activities of the aqueous methanol extract from Acacia nilotica flowers on three human cancer cells, namely lung A549, breast MCF-7, and leukemia THP-1 cells, and (2) the genotoxic effects of A. nilotica extract and its influence on DNA damage induced by N-methyl-N-nitrosourea (MNU) in mice. Methods Mice were orally treated with A. nilotica extract (200, 500, and 800 mg/kg for 4 days) with or without MNU (80 mg/kg intraperitoneally for 24 h). Results In vitro experiments showed that A549 cells were the most sensitive to A. nilotica extract among the tested cell lines. A. nilotica extract inhibited A549 cell proliferation by blocking the cell cycle at the G2/M phase and accumulating apoptotic cells in the sub-G0/G1 phase in A549 cells. In vivo experiments showed that MNU induced positive and negative genotoxicity in bone marrow cells and spermatocytes, respectively. Negative genotoxicity was observed in A. nilotica extract-treated groups only. However, A. nilotica extract (800 mg/kg) remarkably increased comet tail formation in bone marrow cells. Unexpectedly, the absence of antigenotoxicity was observed in three cotreated groups with A. nilotica extract and MNU compared with the MNU-treated group. Astonishingly, cotreatment with MNU and A. nilotica extract at a dose above 200 mg/kg remarkably increased micronucleus and comet tail formation in bone marrow cells compared with the MNU-treated group. Conclusions A. nilotica extract possessed anticancer activity with relative genotoxic effects at high doses.

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“…Omeprazole was delivered 40 mg/100 mL through gavage once a day, and MNNG was supplied in drinking water protected from light in foil packs for free intake. The dose of daily omeprazole was based on the dose for long-term clinical administration in humans (adults, 0.57 mg/kg; children, 0.7 mg/kg) and the metabolic ratio of mouse versus human being [ 50 ], and the MNNG concentration was based on that reported by previous animal experiments [ 51 , 52 ]. Each mouse was weighed once per week after fasting for 12 h without water deprivation, and was deprived of food but allowed free access to water 24 h before sacrifice for specimens.…”

Section: Methodsmentioning

confidence: 99%

Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine

Huang

et al. 2017

Oncotarget

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ObjectivesTo investigate if oral omeprazole application induces cancers of fore and glandular stomach in mice.MethodsA total of 66 eligible male mice were randomly divided into 6 groups, which were treated with control reagent, low (6 mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N’-nitro-N-nitrosoguanidine (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively. After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-β-D-glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in stomach were detected.ResultsThe mouse spleen weight index was smaller in the omeprazole group than the control group, and in the MNNG plus omeprazole groups than the MNNG group. In the fore-stomach, more carcinomas were observed in the MNNG plus omeprazole groups than in the MNNG group. In the glandular stomach, there existed more atypical hyperplasia cases in the MNNG plus omeprazole groups than the MNNG-treated group, and one carcinoma was induced in the MNNG plus high dose omeprazole group. Omeprazole alone caused minor gastric pathological changes. Omeprazole treatment lowered both serum and spleen ACP and NAG levels in both the non-MNNG-treated and MNNG-treated subgroups. In fore-stomach, there existed decreased p21 and mTOR levels in the omeprazole-treated groups than in the control group, and in the MNNG plus omeprazole groups than the MNNG-treated group.ConclusionOmeprazole promotes carcinogenesis of the mouse fore-stomach but not the glandular stomach following treatment with MNNG. Lysosomal hydrolase activity was inhibited and some cancer-associated proteins was dysregulated, which requires further explorations.

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Detection of micronucleated cells and gene expression changes in glandular stomach of mice treated with stomach-targeted carcinogens

Cited by 19 publications

References 19 publications

In vivo comparative studies on antigenotoxicity of date palm (Phoenix dactylifera l.) pits extract against DNA damage induced by N-Nitroso-N-methylurea in mice

In vivo comparative studies on antigenotoxicity of date palm (Phoenix dactylifera l.) pits extract against DNA damage induced by N-Nitroso-N-methylurea in mice

Evaluation of the cytotoxic, anticancer, and genotoxic activities of Acacia nilotica flowers and their effects on N-methyl-N-nitrosourea-induced genotoxicity in mice

Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of nitrosamine

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