The morphological pathway for mouse forestomach cancer

Kossoy, George; Ben‐Hur, Herzl; Elhayany, Asher; Zusman, Itshak

doi:10.3892/or.15.2.479

Cited by 4 publications

(1 citation statement)

References 8 publications

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“…Indeed, the oral exposure to BaP (gavage or diet) has been associated to enhanced tumor responses in lymphoid, hematopoietic, pulmonary, gastric, hepatic, and esophageal tissues in different mouse strains 8 . In the forestomach, the hyperplasia of squamous epithelial cells is considered a preneoplastic condition, as it may progress into benign squamous cell papillomas and invasive/metastatic carcinomas 45 . Although BaP‐induced forestomach tumors in mice are strictly derived from squamous cells whereas most human stomach adenocarcinomas derive from glandular columnar epithelial cells, Labib et al 23 showed striking transcriptomic similarities between BaP‐induced forestomach carcinogenesis and human gastrointestinal tract cancers (including gastric), thus supporting the translational use of this animal model.…”

Section: Discussionmentioning

confidence: 99%

Modifying effects of menthol against benzo(a)pyrene‐induced forestomach carcinogenesis in female Swiss mice

Santo

Romualdo

Santos

et al. 2021

Environmental Toxicology

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Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon widespread in the environment and closely associated to tobacco use, which is an important risk factor for highly incident stomach cancer. Menthol, a monoterpene extracted from Mentha genus species, has multiple biological properties, including anti‐inflammatory and gastroprotective properties, but its effects on carcinogenesis are still to be fully understood. Thus, we evaluated the modifying effects of Ment against BaP‐induced forestomach carcinogenesis. Female Swiss mice received BaP by intragastrical (i.g.) administration (50 mg/kg of body weight [b wt], 2×/week), from weeks 1–5 weeks. Concomitantly, mice received Menthol at 25 (Ment25) or 50 (Ment50) mg/kg b wt (i.g, 3×/week). Animals were euthanized at weeks 5 (n = 5 mice/group) or 30 (n = 10 mice/group). At week 5, both Ment doses reduced peripheral leukocyte blood genotoxicity 4 h after the last BaP administration, but only Ment50 attenuated this biomarker 8 h after the last BaP administration. In accordance to these findings, both Ment interventions attenuated BaP‐induced increase in the percentage of H2A.X‐positive forestomach epithelial cells. Moreover, Ment50 reduced cell proliferation and apoptosis (i.e., Ki‐67 and caspase‐3, respectively) in forestomach epithelium but exerted no significant effects on NFκB, and Nrf2 protein levels. At week 30, Ment50 reduced by ~55% the incidence of BaP‐induced forestomach diffuse hyperplasia and multiplicity of forestomach tumors (squamous cell papillomas and carcinomas). Our findings indicate that Ment50, administered during initiation phase, attenuates forestomach carcinogenesis by reducing early genotoxicity, cell proliferation, and apoptosis induced by BaP.

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Section: Discussionmentioning

confidence: 99%

Modifying effects of menthol against benzo(a)pyrene‐induced forestomach carcinogenesis in female Swiss mice

Santo

Romualdo

Santos

et al. 2021

Environmental Toxicology

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Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

138

100

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Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.

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Serial observations on an orthotopic gastric cancer model constructed using improved implantation technique

Li²,

Xiang³

et al. 2011

WJG

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The morphological pathway for mouse forestomach cancer

Cited by 4 publications

References 8 publications

Modifying effects of menthol against benzo(a)pyrene‐induced forestomach carcinogenesis in female Swiss mice

Modifying effects of menthol against benzo(a)pyrene‐induced forestomach carcinogenesis in female Swiss mice

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Serial observations on an orthotopic gastric cancer model constructed using improved implantation technique

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