Experimental tongue cancer in desalivated rats

Dayar, D; Hirshberg, Abraham; Kaplan, Isaac; Rotem, Nimrod; Bodner, Lipa

doi:10.1016/s0964-1955(96)00048-6

Cited by 52 publications

(59 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…110,111 The addition of 4-NQO to the rat's drinking water has also been shown to reliably induce lingual carcinomas. 112,113,114 Studies agree that murine 4-NQO-induced oral carcinogenesis model simulates many aspects of human oral cavity carcinogenesis. Specifically, on animals in which this carcinogen has been applied, the development of histological atypia increases as the exposure time to 4-NQO increases.…”

Section: 106mentioning

confidence: 75%

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

Smith

Thomas

2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Understanding the complex histological, genetic and molecular changes that lead to malignant transformation of squamous epithelia of the head and neck will likely guide the development of methods for improved diagnosis, monitoring and treatment of head and neck squamous cell carcinoma (HNSCC). The development and use of animal models that closely mimic the histopathology and molecular pathogenesis of HNSCC in humans would greatly expand the research possibilities and provide a means of testing potential therapeutic agents. However, many available animal models of HNSCC fall short of this objective. In order for investigators to select the appropriate model to answer scientific questions, it is important to understand the benefits and limitations of available animal models for the study of HNSCC. The purpose of this work is to give an overview of the most pertinent animal models of HNSCC, and to discuss future directions of research in this field. ' 2005 Wiley-Liss, Inc.Head and neck squamous cell carcinoma (HNSCC) involves the upper aerodigestive tract and can destroy the structure and function of organs involved in voice, speech, taste, smell and hearing, as well as vital structures necessary for survival. Approximately half of all patients with HNSCC have advanced stage disease at the time of diagnosis, with an expected 5-year survival rate between 10 and 40%.1 Despite treatments that may consist of mutilating surgery, radiotherapy and/or chemotherapy, overall long-term survival remains low due to uncontrollable persistent or recurrent disease. The survival rate of patients with locoregional and distant recurrences has highlighted the need for new approaches for diagnosis and treatment. To this end, a better understanding of the genetic, molecular and immunoregulatory processes leading to neoplastic transformation and progression of HNSCC is needed, so that novel and more effective diagnostic and therapeutic approaches can be designed.Although in vitro study systems are useful for studying the interactions between different cell populations in culture and are convenient and simple to use, they do not reproduce the complexity of HNSCC. For this reason, the development of new therapies will require clinically relevant animal models of HNSCC. Adequate animal models are necessary to test the translational potential of preventive and therapeutic agents, as well as to understand the biological mechanisms of epithelial carcinogenesis and progression. The ideal experimental animal tumor model for HNSCC must reproduce the characteristic features of the disease, including the complicated patterns of tumor-host interactions such as immune response, angiogenesis, invasion and metastasis. In the ideal model, clinical symptoms and laboratory abnormalities should be similar to the human disease and therapeutic agents should be as effective in both systems. The ideal model must also be easy to use, accessible to genetic and immunologic manipulations, reproducible and progress rapidly to allow timely investigations.Animal mod...

show abstract

Section: 106mentioning

confidence: 75%

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

Smith

Thomas

2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Peroxidase is by far the most important antioxidant enzyme in the OP cavity, and as such theoretically serves as the first line of anticarcinogenic defense against free radical-induced OP cancer. It is interesting to note that the possible role of saliva as an anticarcinogenic medium was recently demonstrated in an animal study in which oral cancer was induced by a local carcinogen, 4NQO (Nishioka et al, 1981;Dayan et al, 1997). Further credence for salivary anticarcinogenic protective capacity was given by Nishioka et al (1981) who, using the Ames test, found that saliva inhibited the mutagenicity of another well-known local oral cancer inducer, benzopyrene (Figure 10).…”

Section: Discussionmentioning

confidence: 94%

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

2004

View full text Add to dashboard Cite

Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy and accounts for 2 -4% of all new cancers. It is primarily induced by exposure to tobacco. The paradigm of cigarette smoke (CS)-induced OP cancer's pathogenesis is based on the assumption that a constant direct attack of various CS carcinogens causes widespread accumulating cellular and DNA aberrations in the OP mucosal cells, in turn eventually resulting in malignant transformation. However, there is never a direct contact between CS and the OP mucosa. Saliva, bathing the mucosa from the oral cavity to the larynx, always intervenes, and CS must first interact with saliva before it reaches the mucosa. The current study investigated the role of saliva in the pathogenesis of OP cancer. A synergistic effect of CS and saliva on oral cancer cells was demonstrated. This synergism is based on the reaction between redox active metals in saliva and low reactive free radicals in CS, which results in the production of highly active hydroxyl free radicals. Thus, when exposed to CS, salivary behavior is reversed and the saliva loses its antioxidant capacity and becomes a potent prooxidant milieu. The devastating role of CS-borne aldehydes was demonstrated as well. Based on these results and on our recent reports demonstrating that CS destroys various salivary components, including protective ones such as peroxidase, the most important salivary antioxidant enzyme, a comprehensive view of the pivotal role of saliva in the pathogenesis of CS-induced OP cancer is suggested. Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy, having a worldwide incidence of over 300 000 new cases each year and accounting for 2 -4% of all new cancers (Bross and Coombes, 1976;McGinnis and Foege, 1993;Collins et al, 1994;Ko et al, 1995;Piyathilake et al, 1995;Zheng et al, 1997;Nagler et al, 1999; Lippman and Hong, 2001). The commonly accepted paradigm for cigarette smoke (CS)-induced OP cancer pathogenesis is based on the assumption that a constant and direct attack of various CS carcinogens causes widespread accumulating cellular and DNA aberrations in the OP mucosa eventually leading to malignant transformation and cancer development. The CS-borne carcinogens are often thought to be free radicals. The process is initially expressed by dysplastic mucosal lesions which are then transformed into in situ carcinoma lesions, eventually resulting in fullblown infiltrating and metastasising OP cancer (Holleb et al, 1991). Chen et al (2002) demonstrated that chewing tobacco (areca quid) resulted in the formation of ROS in the oral cavity causing oxidative DNA damage to the surrounding tissues. Further support can be found in a report demonstrating that premalignant mucosal lesions and low-grade carcinomas express DNA aberrations following a pathway of exposure to free radicals (Sudb et al, 2001). Moreover, Bloching et al (2001) recently found increased genotoxic activity in the saliv...

show abstract

“…1). OSCC was induced as described previously (16,17). Briefly, mice were treated with a solution of 100 µg/ml propylene glycol/4-NQO (Sigma-Aldrich, St. Louis, MO, USA) in drinking water for 16 weeks.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

“…The use of 4-NQO is a valuable technique for inducing OSCC, and induces carcinogenesis in animal models in a manner similar to the natural progression of OSCC in humans (17,18). 4-NQO is a water-soluble quinoline derivative and is known to form DNA adducts.…”

Section: A B Cmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

Abstract. Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer, and oxidative damage is associated with the development of OSCCs. Antioxidants have therefore been proposed for use as chemoprotective agents against different types of cancer. In the present study, the effect of the antioxidant quercetin, administered at doses of 10 and 100 mg/kg/day, was investigated in an experimental murine model of 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis. The survival of the treated animals, the plasmatic levels of reduced glutathione and the type and severity of lesions (according the International Histological Classification of Tumors and Bryne's Multifactorial Grading System for the Invasive Tumor Front) were assessed. Additionally, the organization of the extracellular matrix was analyzed by carbohydrate and collagen histochemistry, and immunohistochemistry was used to assess the expression of the tumor markers proliferating cell nuclear antigen and mutated p53. The results indicate that, despite the promising effect of quercetin in other studies, this drug is ineffective as a chemoprotective agent against 4-NQO-induced OSCC in mice at the assayed doses.

show abstract

Experimental tongue cancer in desalivated rats

Cited by 52 publications

References 12 publications

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

Contact Info

Product

Resources

About