4-Nitroquinoline 1-Oxide-Induced Tongue and Esophagus Carcinogenesis in Obese and Diabetic TSOD Mice
Bibliographic record
Abstract
BACKGROUND: Obesity and diabetes mellitus are associated with lifestyle-related carcinogenesis. They are also risk factors of esophageal adenocarcinoma, but there are only a few reports on association between obesity/diabetes and development of squamous cell carcinoma in the oral cavity and esophagus. In this study, we therefore aimed to determine whether obesity and diabetes affect oral and esophageal carcinogenesis using model mice of obesity and diabetes, the Tsumura Suzuki obese diabetes (TSOD) and Tsumura Suzuki non-obesity (TSNO) control mice, which were treated with 4-nitroquinoline 1-oxide (4-NQO) to produce tongue and esophageal carcinomas. METHODS: We used 28 each of the male TSOD and TSNO mice of 8 weeks of age. They were divided into the 4-NQO-treated group (n = 20) and untreated group (n = 8). 4-NQO was administered to mice in drinking water at a dose level of 20 ppm for 8 weeks. The untreated group was given distilled water without 4-NQO. At 28 experimental weeks, histopathological examination was performed on all organs including tongue and esophagus. We performed analysis of histopathology of all organs which included buccal capsule (a tongue)/esophagus after an experiment start in 28 weeks. Fasting plasma glucose (FPG) and lipid parameters including total cholesterol (T-Cho), triglyceride (TG), high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were measured and all these parameters were compared between the two genotypes. Also, mRNA expression of eight cytokines including interleukin (IL)-1β, IL-6, IL-17, interferon (IFN)-γ, keratinocyte-derived cytokine (KC), macrophage inflammatory protein (MIP)-1α, MIP-2, and tumor necrosis factor (TNF)-α in the esophageal mucosa was assayed. RESULTS: 4-NQO treatment produced proliferative squamous cell lesions (dysplasia, papilloma and carcinoma) in the tongue and esophagus of both the TSOD and TSNO mice. The incidence and multiplicity of tongue tumors were 30% and 0.45 ± 0.83 in the TSOD mice and 30% and 0.40 ± 0.68 in the TSNO mice. The incidence and multiplicity of esophageal tumors were 70% and 2.25 ± 2.29 in the TSOD mice and 30% and 0.60 ± 1.14 (P < 0.01) in the TSNO mice. CONCLUSION: Our findings indicate that the obese and diabetic TSOD mice were susceptible to 4-NQO-induced esophageal carcinogenesis, suggesting risk factors of obese and diabetes for esophageal squamous cell carcinoma. Additionally, the TSOD mice were useful as esophagus carcinogenic model. Our study first reported that 4-NQO induced esophageal cancer in mice.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".