Dietary fat and male sex increase histopathological changes in a mouse model of oral cancer

Green, Jacalyn M.; Ciancio, Mae J.; Góral, Joanna; Pytynia, Matthew; Pitstick, Lenore; Meyer, A.; Nguyen, Andrew; Lee, Katherine; Barakat, Ameir; Jham, Bruno Correia

doi:10.1111/odi.13542

Cited by 5 publications

(9 citation statements)

References 53 publications

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“…Therefore, none of the experimental animals developed tumors that, due to their size, would mandate euthanizing the animal. This was further confirmed by the 24-hour food intake measurement performed at week 19 of the study that did not show any significant reduction in calorie consumption in 4NQO-treated when compared to control mice [ 34 ].…”

Section: Resultsmentioning

confidence: 76%

“…In this study we aimed to investigate whether administration of the chemical carcinogen 4NQO would cause hepatic pathology in an established mouse model of oral cancer. 4NQO, when administered in the drinking water, caused oral squamous cell carcinoma in all mice that completed the protocol [ 34 ]. This chemical carcinogen causes changes in oral tissues in a manner analogous to changes caused by tobacco exposure.…”

Section: Resultsmentioning

confidence: 99%

“…While this study investigated the effects of 4NQO on livers in male and female mice on a HF diet or LF diet, a previous study focused upon the tongues from the same animals [ 34 ]. All 4NQO-treated mice developed tumors in the oral cavity, which is not surprising given that this is an established model of oral cancer.…”

Section: Discussionmentioning

confidence: 99%

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Fat and exposure to 4-nitroquinoline-1-oxide causes histologic and inflammatory changes in murine livers

et al. 2022

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Risk factors for liver cancer include tobacco use, alcohol consumption, obesity, and male sex. Administration of 4-nitroquinonline-1-oxide (4NQO) in drinking water mimics the effects of tobacco and leads to oral carcinoma in mice. This study compared the effects of diets high and low in saturated fat (HF and LF, respectively), and sex, on liver histopathology in 4NQO-treated mice and controls. We hypothesized that 4NQO would cause histopathological changes in liver, and that a HF diet would increase hepatic pathology when compared to the LF diet. Mice (C57Bl/6, 36/sex), were divided into a low fat (10 kcal% fat; LF) or high fat (60 kcal% fat, HF) diet. Mice were further subdivided into one of 3 water treatment groups for 17 weeks: water (control), vehicle (1.25% propylene glycol in water [PG]), or 4NQO in (50 μg/ml; 4NQO). All mice were subsequently given water alone for 6 more weeks. Upon euthanasia, livers were harvested, fixed, sectioned, and stained with hematoxylin and eosin (H&E). H&E slides were graded for histopathology; frozen liver samples were analyzed for triglyceride content. Trichrome stained sections were graded for fibrosis. CD3+ T cells, CD68+ macrophages, and Ly6+ neutrophils were detected by immunohistochemistry. Compared to water controls, 4NQO-treatment caused mouse liver histopathological changes such as fibrosis, and increases in hepatic neutrophils, T cells, and macrophages. HF diet exacerbated pathological changes compared to LF diet. Male controls, but not females, demonstrated severe steatosis and increased triglyceride content. 4NQO treatment decreased hepatic fat accumulation, even in animals on a HF diet. In conclusion, this murine model of oral cancer may serve as a model to study the effects of tobacco and diet on liver.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

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Fat and exposure to 4-nitroquinoline-1-oxide causes histologic and inflammatory changes in murine livers

et al. 2022

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“…In this study, we aimed to examine the effects of a diet sufficient in dietary folate compared to a diet deficient in dietary folate, as well as the effects of sex on the incidence and severity of oral SCC in the well-characterized 4NQO-induced murine model of oral SCC (Schoop et al, 2009). Previous studies in our laboratory demonstrated the influence of sex and dietary fat intake on 4NQO-induced oral SCC, demonstrating increased total tumor burden in male mice and mice fed a 60 kcal% fat diet compared to female mice and mice fed a 10 kcal% diet (Green et al, 2021). In the current study, immunohistochemistry was used to compare expression of folate transport proteins (reduced folate carrier, folate receptor, and proton-coupled folate transporter), as well as to evaluate cellular proliferation as measured by the presence of Ki67+ cells (Gerdes, 1990).…”

Section: Introductionmentioning

confidence: 91%

Effects of folate deficiency and sex on carcinogenesis in a mouse model of oral cancer

Pitstick,

Goral,

Ciancio

et al. 2023

Oral Diseases

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ObjectivesTo investigate the effects of dietary folate and sex on histopathology of oral squamous cell carcinoma in mice.Materials and MethodsMice (C57Bl/6, 30/sex) were fed either a deficient folate or sufficient folate diet. Vehicle or 4‐nitroquinoline1‐oxide (50 μg/mL) in vehicle were administered in drinking water for 20 weeks, followed by 6 weeks of regular drinking water. Oral lesions were observed weekly. Tongues were studied for histopathologic changes. Immunohistochemical techniques were used to measure cell proliferation (Ki67+), and to quantify expression of folate receptor, reduced folate carrier, and proton‐coupled folate transporter. T cells, macrophages, and neutrophils were counted and normalized to area.ResultsAll 4NQO‐treated mice developed oral tumors. Dietary folate level did not affect tumor burden. More tumors were observed on the ventral aspect of the tongue than in other locations within the oral cavity. 4‐nitroquinoline‐1‐oxide‐treated mice displayed 27%–46% significantly lower expression of all three folate transport proteins; diet and sex had no effect on folate transporter expression. T‐cell and neutrophil infiltration in tongues were 9.1‐fold and 18.1‐fold increased in the 4‐nitroquinoline‐1‐oxide‐treated mouse tongues than in controls.ConclusionTreatment with 4NQO was the primary factor in determining cancer development, decreased folate transport expression, and lymphoid cell infiltration.

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“…Consumption of minimally processed foods has been reported as a protective factor in the development of squamous cell carcinoma of the head and neck [98]. An in vivo mouse model demonstrated that a high-fat diet and male sex contribute to the pathology of 4-nitroquinoline-1-oxideinduced oral cancer [99]. An important dietary risk factor for the development of OSCC is the high intake of iron linked to the involvement of this element in major cellular processes, such as metabolism, cell growth, and proliferation, with the generation of nitrogen compounds and free radicals, which cause cell damage [100].…”

Section: Diet and Nutritionmentioning

confidence: 99%

The World of Oral Cancer and Its Risk Factors Viewed from the Aspect of MicroRNA Expression Patterns

Aghiorghiesei

Zănoagă

Nuțu

et al. 2022

Genes

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Oral cancer is one of the leading causes of death worldwide, with a reported 5-year survival rate of around 50% after treatment. Epigenetic modifications are considered to have a key role in oral carcinogenesis due to histone modifications, aberrant DNA methylation, and altered expression of miRNAs. MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in cancer development by regulating signaling pathways involved in carcinogenesis. MiRNA deregulation identified in oral cancer has led to the idea of using them as potential biomarkers for early diagnosis, prognosis, and the development of novel therapeutic strategies. In recent years, a key role has been observed for risk factors in preventing and treating this malignancy. The purpose of this review is to summarize the recent knowledge about the altered mechanisms of oral cancer due to risk factors and the role of miRNAs in these mechanisms.

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Dietary fat and male sex increase histopathological changes in a mouse model of oral cancer

Cited by 5 publications

References 53 publications

Fat and exposure to 4-nitroquinoline-1-oxide causes histologic and inflammatory changes in murine livers

Fat and exposure to 4-nitroquinoline-1-oxide causes histologic and inflammatory changes in murine livers

Effects of folate deficiency and sex on carcinogenesis in a mouse model of oral cancer

The World of Oral Cancer and Its Risk Factors Viewed from the Aspect of MicroRNA Expression Patterns

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