Arecoline tumorigenicity in swiss strain mice on normal and vitamin B deficient diet

Bhide, S. V.; Gothoskar, S. V.; Shivapurkar, NM

doi:10.1007/bf01032602

Cited by 21 publications

(10 citation statements)

References 10 publications

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“…The oral LD 50 value of arecoline in swiss albino male mice was 371 mg/kg [22]. A tumorigenicity study in swiss strain mice showed that arecoline treatment induced tumors in 43% of males at a dosage of 5 mg/animal/week (p.o) throughout their life-span [23]. Arecoline was positive in the mouse bone marrow micronucleus test at a dose of 2 mg/animal (i.p) administered twice [17].…”

Section: Discussionmentioning

confidence: 98%

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice

Xing

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Section: Discussionmentioning

confidence: 98%

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice

Xing

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…However, arecoline has also been associated with the development of oral premalignant lesions and risk of oral cancer in many areas of Asia, the Pacific region, and in migrant communities in the United Kingdom, United States and South Africa where betel chewing is prevalent (Gupta and Warnakulasuriya, 2002; Sharan et al, 2012). Several animal studies have shown that arecoline administered by oral gavage to male mice induced lung adenocarcinoma and liver hemangioma (Bhide et al, 1984; Bhide et al, 1979), and chronic oral administration of arecoline through drinking water resulted in oral squamous cell carcinoma in mice (Lin et al, 2015b). However, arecoline was found not mitogenic to oral mucosal fibroblasts, and it causes cell cycle arrest of cultured oral KB epithelial cells (Chang et al, 2001; Tsai et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth

et al. 2016

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SUMMARY Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is “hijacked” to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers but not monomers are phosphorylated and stabilized by enhanced Y407-phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor, which binds to and disrupts only ACAT1 tetramers. The resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of tetrameric ACAT1 by abolishing Y407-phosphorylation or AH treatment results in decreased ACAT1 activity, leading to increased PDC flux and oxidative phosphorylation with attenuated cancer cell proliferation and tumor growth. These findings provide a mechanistic understanding of how oncogenic events signal through distinct acetyltransferases to regulate cancer metabolism, and suggest ACAT1 as an anti-cancer target.

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“…The lime (calcium hydroxide) used can result in an alkaline pH, triggering ROS release and causing irritation of the oral mucosa and hyperplasia [ 55 ]. Areca nut consists of phenolic compounds, and tobacco releases various nitrosamines in the mouth that are responsible for proliferative abrasions and damage to DNA and fibroblasts [ 42 , 56 ].…”

Section: Mechanism Of Genotoxicity and Carcinogenicitymentioning

confidence: 99%

“… Initial events in the pathogenesis of mouth cancer [ 56 , 63 ]. IL-6, interleukin-6; If-α, interferon-alpha; TNF, tumor necrosis factor; TGF-β, transforming growth factor-beta.…”

Section: Figurementioning

confidence: 99%

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer

et al. 2017

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The term "smokeless tobacco" refers to the consumption of unburned tobacco, in the form of chewing, spitting, dipping, and snuff. Consumers chew the tobacco in the mouth and spit out the juice that builds up. Nicotine and other constituents are absorbed in the lining of oral cavity. People of many regions, including India, Pakistan, other Asian countries, and North America, have a long history of smokeless tobacco use. Approximately 28 chemical constituents present in smokeless tobacco are carcinogenic in nature, among which nitrosamine is the most prominent [1].People mostly use paan and gutkha due to a lack of awareness and education. They are not aware of the harmful effects associated with the use of these substances, and it has been reported that these products are consumed for perceived beneficial effects, such as mouth freshening, aid in digestion, germ-killing, astringency, mood enhancement, tension relief, and oral cleaning [1]. Gutkha is sweet in taste, and children consider it to be a form of candy. Many people believe that gutkha is a mouth freshener, but its pleasant taste and sweetness aggregate microbes, causing damage to teeth. The use of paan and gutkha is difficult to control in most countries where it is widespread, and their extensive use leads to oral cancer [2]. The consumption of smokeless tobacco and areca nut is high in South Asian countries in the form of paan. In various South Asian languages, paan simply means "leaf. " Various inSmokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eve...

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Arecoline tumorigenicity in swiss strain mice on normal and vitamin B deficient diet

Cited by 21 publications

References 10 publications

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice

Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer

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