The genotoxic potential of nicotine and its major metabolites

Doolittle, David J.; Winegar, Richard A.; Lee, C K; Caldwell, William S.; Hayes, A. Wallace; deBethizy, J D

doi:10.1016/0165-1218(95)00037-2

Cited by 97 publications

(41 citation statements)

References 20 publications

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“…There also is evidence that nicotine may promote metastasis because of stimulation of cell motility and migration (13,18). Although nicotine may be able to form DNA adducts, it generally is not genotoxic (27)(28)(29)(30)(31)(32)(33). Taken together, these studies support the hypothesis that nicotine could enhance carcinogenesis and raise a concern that nicotine could promote carcinogenesis in former smokers, who have a background of initiated cells with genetic damage left over from the earlier smoking days.…”

supporting

confidence: 73%

Long-term Nicotine Replacement Therapy: Cancer Risk in Context

Shields

2011

Cancer Prevention Research

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Nicotine replacement therapy (NRT) for up to 12 weeks is well established, safe and efficacious for fostering smoking cessation. Some smokers at a high risk of relapse may benefit from long-term use, and so long-term NRT safety and efficacy have become a paramount question for the FDA and others. Laboratory studies have indicated a carcinogenic potential of nicotine. Animal model studies reported in this issue of the journal by Maier and colleagues (beginning on page 1743) and Murphy and colleagues (beginning on page 1752), however, provide additional reassurance that NRT does not promote lung cancer. Very long-term studies of NRT effects do not yet exist and would be needed to definitively answer the question about NRT efficacy and cancer risk and some decision making will need to be made based on limited human data and experimental studies. The overall NRT safety question is complex and requires consideration of three contexts and comparator groups (long-term NRT/abstinence vs. smoking, long-term intermittent NRT/ reduced smoking vs. smoking, and long-term NRT/abstinence vs. abstinence without long-term NRT). Although the data on these issues are insufficient, the first comparison seems intuitive and may be compelling enough to allow the FDA to approve a long-term indication for NRT. An important public health goal is to help smokers and their health care providers understand the implications of potential long-term NRT risks in the context of its potential benefits and the far greater risks of continued smoking. Cancer Prev Res; 4(11); 1719-23. Ó2011 AACR.The efficacy and safety of short-term nicotine replacement therapy (NRT) for fostering long-term smoking cessation is well established, and up to 12 weeks of therapy is approved by the U.S. Food and Drug Administration (FDA; refs. 1-4). A meta-analysis indicates that there are measurable benefits in studies of 12 to 18 months of continued NRT use for relapse prevention (5), and other studies also indicate that this use is cost effective (6). An important question of considerable interest that remains today, however, is whether NRT can be recommended for long-term use, even years, to continue to promote smoking abstinence. The answer to this question requires both an efficacy and safety assessment. In this context, NRT conceptually has substantial benefits compared with long-term smoking but also, as explained later and addressed in this issue of the journal, laboratory studies suggest a potential for nicotine to foster the development of cancer.The premise of long-term NRT use is that it would prevent smoking relapse, and the risks would be limited to maintaining nicotine addiction, but without the adverse consequences of continued smoking, such as increased lung cancer risk. Like the consideration of other long-term medications, on face value it is a simple risk-benefits equation. In actuality, however, this question is not simple to answer because the risk can be considered in 3 different contexts and comparator groups namely: (i) what is the risk o...

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supporting

confidence: 73%

Long-term Nicotine Replacement Therapy: Cancer Risk in Context

Shields

2011

Cancer Prevention Research

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“…Alteration of heat shock protein production Hahn et al 1991), inhibition of cell metabolism and proliferation (Konno et al 1991;Waggoner and Wang 1994), and induction of nuclear aberrations (Livingstone et al 1990;Doolittle et al 1995) are some of the common results of smokeless tobacco extract and nicotine administration. In addition, it has been demonstrated that both nicotine and smokeless tobacco administration result in generation of reactive oxygen species in in vitro experimental systems Wetscher et al 1995a).…”

mentioning

confidence: 99%

Comparison of Pure Nicotine- and Smokeless Tobacco Extract-Induced Toxicities and Oxidative Stress

Yıldız

Liu

Erçal

et al. 1999

Archives of Environmental Contamination and Toxicology

111

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Abstract. The toxicities and oxidative stress-inducing actions of (Ϫ)-nicotine and smokeless tobacco extract (STE), containing equivalent amounts of nicotine, were studied. Toxicities were determined by colony formation assays using Chinese hamster ovary (CHO) cells. Results indicated that nicotine is less toxic than smokeless tobacco extract that contained the same amount of nicotine. The generation of reactive oxygen species, following treatment with smokeless tobacco extract and nicotine, was assessed by measurement of changes in glutathione (GSH) and malondialdehyde (MDA) levels. CHO cells (5 ϫ 10 5 cells/5 ml media) were incubated with 4, 0.8, and 0.08 mg of nicotine and STE containing the same amounts of nicotine. All preparations of smokeless tobacco extract significantly decreased GSH levels and increased MDA generation. However, 0.08 mg of nicotine treatment did not result in a significant change in GSH level, and only 4 mg of nicotine were sufficient to increase MDA generation. Addition of free radical scavenging enzymes, superoxide dismutase (SOD) and catalase (CAT), and an intracellular GSH precursor, N-acetyl-L-cysteine (NAC), replenished the GSH levels in nicotine-treated cells. GSH levels in cells exposed to smokeless tobacco extract containing 4 and 0.8 mg nicotine remained significantly lower than the control with the addition of SOD and CAT. However, co-addition of NAC with smokeless tobacco extract preparations returned the GSH levels to the control level. Lactate dehydrogenase (LDH) activities were measured in the media to establish the membrane damage following exposure to smokeless tobacco extract and nicotine. Treatment of cells with 4 mg nicotine caused a significant increase in LDH activity, which was returned to control level in the presence of the antioxidant enzymes and NAC. Smokeless tobacco extract did not change the LDH activity.

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“…10 Ekstrak daun tembakau mengandung bahan utama yaitu nikotin. 11 Dalam hal nikotin yang terhirup, akan mencapai otak dan mengaktivasi reseptor asetilkolin nikotinik (nAChR) yang tersebar pada sistem saraf pusat dan perifer serta jaringan perifer lainya. 12 Efek pada otak adalah meningkatkan neurotransmiter terutama dopamin yang mengakibatkan efek adiksi terhadap nikotin.…”

Section: Pembahasanunclassified

EKSTRAK DAUN Nicotiana tabacum MENURUNKAN BERAT LEMAK VISCERAL PADA TIKUS DIABETES MELLITUS TIPE DUA

Suprapto

Jonathan²,

Ernanda³

et al. 2017

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AbstrakDiabetes mellitus merupakan masalah utama kesehatan di dunia dan prevalensinya selalu meningkat. Pada dosis yang tepat kandungan nikotin dari ekstrak etanol daun tembakau (Nicotiana tabacum) memiliki efek hipoglikemik sehingga berpeluang sebagai terapi alternatif untuk diabetes mellitus. Namun, efeknya pada jaringan adipose penderita diabetes mellitus belum banyak diketahui. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh ekstrak etanol daun tembakau terhadap berat lemak visceral tikus model diabetes mellitus. Pada penelitian ini tikus galur Wistar dibagi menjadi 5 kelompok yaitu kontrol negatif (K-), kelompok tikus model diabetes mellitus (K+), dan tiga kelompok tikus diabetes melitus yang diberi ekstrak etanol daun tembakau 90 (P1), 180 (P2) dan 270 (P3) mg/kgBB/hari per oral selama 28 hari. Hasil penelitian menunjukkan bahwa terdapat penurunan bermakna berat lemak pada semua kelompok tikus DM yang diberi ekstrak daun tembakau dibandingkan dengan tikus DM tanpa terapi maupun tikus normal (p < 0,05). Kesimpulan penelitian adalah pemberian ekstrak etanol daun tembakau menurunkan berat lemak visceral pada tikus model DM. Penurunan berat lemak visceral kemungkinan disebabkan oleh kandungan nikotin dalam ekstrak yang dapat mengaktivasi lipolisis, menghambat lipogenesis, aktivasi thermogenesis, dan penurunan intake makan.Kata kunci: berat lemak visceral, diabetes mellitus, daun tembakau (Nicotiana tabacum). ETHANOL EXTRACT OF Nicotiana tabacum REDUCES THE VISCERAL WEIGHT OF TYPE TWO DIABETIC RATS AbstractDiabetes melllitusis the main health problem in the world and its prevalence is increasing dramatically. Tobacco leaf (Nicotiana tabacum) containing nicotine could be used as an alternative treatment for diabetes mellitus at the right dose. However, its effect on adipose tissue of diabetes mellitus model has not established well. This study aim is to observe the effect of ethanol extract of tobacco leaf to the visceral weight of diabetic rats. Rats were divided into five group normal rats (K-), diabetic rats (K+) and diabetic rats receiving ethanol extract of tobacco leaf at dose 90 (P1), 80 (P2), and 270 (P3) mg/kgBW/day orally for 28 days. Rats were sacrificed and visceral fat was weighed afterward. As the result, visceral fat of diabetic rats was less than the normal rats and diabetic rats treated with ethanol extract of tobacco leaf shown to reduce visceral weight significantly compared to normal rats (p < 0.05). Visceral weight decrement was due to nicotine effect that could induce lipolysis, inhibit lipogenesis, thermogenesis activation, and reduce food intake. Further research is needed to explore Nicotiana tabacum as an alternative treatment for diabetes mellitus.

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The genotoxic potential of nicotine and its major metabolites

Cited by 97 publications

References 20 publications

Long-term Nicotine Replacement Therapy: Cancer Risk in Context

Long-term Nicotine Replacement Therapy: Cancer Risk in Context

Comparison of Pure Nicotine- and Smokeless Tobacco Extract-Induced Toxicities and Oxidative Stress

EKSTRAK DAUN Nicotiana tabacum MENURUNKAN BERAT LEMAK VISCERAL PADA TIKUS DIABETES MELLITUS TIPE DUA

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