Identification of tobacco-derived compounds in human pancreatic juice

Bogdan Prokopczyk, Dietrich Hoffmann, Matthew Bologna, A. John Cunningham, Neil Trushin, Shobha Akerkar, Telih Boyiri, Shantu Amin, Dhimant Desai, Stephen Colosimo, Brian Pittman, Gerhard Leder, Marco Ramadani, Doris Henne-Bruns, Hans G. Beger, Karam El-Bayoumy

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Abstract

Cancer of the pancreas is the fourth leading cause of cancer mortality in the USA with an estimated 28 900 deaths in 2001. Several factors have been implicated in the etiology of this disease. However, at present, only cigarette smoking has been positively associated with pancreatic cancer. It is our working hypothesis that tobacco-derived compounds can be delivered to the pancreas where, upon metabolic activation, they can initiate carcinogenesis. Our current investigation was conducted to determine whether cotinine and tobacco-specific nitrosamines (TSNA) are present in human pancreatic juice. Smoking status was assessed by the determination of levels of urinary cotinine and was further supported by quantifying nicotine in hair. The TSNA were extracted from the pancreatic juice of 18 smokers and 9 nonsmokers by supercritical carbon dioxide that contained 10% methanol. The extracts were analyzed for TSNA, namely, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN), by gas chromatography with mass spectrometric detection using a selected ion monitoring technique (GC-SIM-MS). Twenty-three extracts of human pancreatic juice were also analyzed for the presence of the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by GC-SIM-MS and by gas chromatography interfaced wit a thermal energy analyzer (GC-TEA; TEA, a nitrosamine-specific detector). Cotinine was detected in all analyzed samples of pancreatic juice from smokers (129 ± 150 ng/mL juice; mean ± standard deviation) and was present in only two of the nine samples of pancreatic juice from nonsmokers. Its levels in these two samples were 7 and 9 ng/mL juice. NNK was detected in 15 of 18 samples (83%) from smokers at levels from 1.37 to 604 ng/mL pancreatic juice. In nine samples of pancreatic juice from nonsmokers, NNK ranged from not detected (in three samples) to 96.8 ng/mL juice. In pancreatic juice from smokers the mean level of NNK (88.7 ± 161 ng/mL juice) was significantly higher (p < 0.04) than in that from nonsmokers (12.4 ± 31.7 ng/mL juice). In addition to NNK, NNN was found in two samples of pancreatic juice of smokers at levels of 68.1 and 242 ng/mL juice; NNN was not detected in any other sample. NNAL was present in 8 of 14 pancreatic juice samples (57%) from smokers and in three of nine samples (33%) from nonsmokers. This research presents preliminary data that supports the hypothesis that pancreatic tissue is exposed to TSNA and that they may be important contributors to pancreatic carcinogenesis in humans.

Original languageEnglish (US)
Pages (from-to)677-685
Number of pages9
JournalChemical Research in Toxicology
Volume15
Issue number5
DOIs
StatePublished - May 30 2002

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N'-nitrosonornicotine
Pancreatic Juice
Nitrosamines
Tobacco
Cotinine
Gas chromatography
Metabolites
Thermal energy
Pancreatic Neoplasms
Nicotine
Carbon Dioxide
Tobacco Products
Gas Chromatography
Methanol
Carcinogenesis
Smoking
Chemical activation
Ions
Tissue
Detectors

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Prokopczyk, B., Hoffmann, D., Bologna, M., Cunningham, A. J., Trushin, N., Akerkar, S., ... El-Bayoumy, K. (2002). Identification of tobacco-derived compounds in human pancreatic juice. Chemical Research in Toxicology, 15(5), 677-685. https://doi.org/10.1021/tx0101088
Prokopczyk, Bogdan ; Hoffmann, Dietrich ; Bologna, Matthew ; Cunningham, A. John ; Trushin, Neil ; Akerkar, Shobha ; Boyiri, Telih ; Amin, Shantu ; Desai, Dhimant ; Colosimo, Stephen ; Pittman, Brian ; Leder, Gerhard ; Ramadani, Marco ; Henne-Bruns, Doris ; Beger, Hans G. ; El-Bayoumy, Karam. / Identification of tobacco-derived compounds in human pancreatic juice. In: Chemical Research in Toxicology. 2002 ; Vol. 15, No. 5. pp. 677-685.
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abstract = "Cancer of the pancreas is the fourth leading cause of cancer mortality in the USA with an estimated 28 900 deaths in 2001. Several factors have been implicated in the etiology of this disease. However, at present, only cigarette smoking has been positively associated with pancreatic cancer. It is our working hypothesis that tobacco-derived compounds can be delivered to the pancreas where, upon metabolic activation, they can initiate carcinogenesis. Our current investigation was conducted to determine whether cotinine and tobacco-specific nitrosamines (TSNA) are present in human pancreatic juice. Smoking status was assessed by the determination of levels of urinary cotinine and was further supported by quantifying nicotine in hair. The TSNA were extracted from the pancreatic juice of 18 smokers and 9 nonsmokers by supercritical carbon dioxide that contained 10{\%} methanol. The extracts were analyzed for TSNA, namely, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN), by gas chromatography with mass spectrometric detection using a selected ion monitoring technique (GC-SIM-MS). Twenty-three extracts of human pancreatic juice were also analyzed for the presence of the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by GC-SIM-MS and by gas chromatography interfaced wit a thermal energy analyzer (GC-TEA; TEA, a nitrosamine-specific detector). Cotinine was detected in all analyzed samples of pancreatic juice from smokers (129 ± 150 ng/mL juice; mean ± standard deviation) and was present in only two of the nine samples of pancreatic juice from nonsmokers. Its levels in these two samples were 7 and 9 ng/mL juice. NNK was detected in 15 of 18 samples (83{\%}) from smokers at levels from 1.37 to 604 ng/mL pancreatic juice. In nine samples of pancreatic juice from nonsmokers, NNK ranged from not detected (in three samples) to 96.8 ng/mL juice. In pancreatic juice from smokers the mean level of NNK (88.7 ± 161 ng/mL juice) was significantly higher (p < 0.04) than in that from nonsmokers (12.4 ± 31.7 ng/mL juice). In addition to NNK, NNN was found in two samples of pancreatic juice of smokers at levels of 68.1 and 242 ng/mL juice; NNN was not detected in any other sample. NNAL was present in 8 of 14 pancreatic juice samples (57{\%}) from smokers and in three of nine samples (33{\%}) from nonsmokers. This research presents preliminary data that supports the hypothesis that pancreatic tissue is exposed to TSNA and that they may be important contributors to pancreatic carcinogenesis in humans.",
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Prokopczyk, B, Hoffmann, D, Bologna, M, Cunningham, AJ, Trushin, N, Akerkar, S, Boyiri, T, Amin, S, Desai, D, Colosimo, S, Pittman, B, Leder, G, Ramadani, M, Henne-Bruns, D, Beger, HG & El-Bayoumy, K 2002, 'Identification of tobacco-derived compounds in human pancreatic juice', Chemical Research in Toxicology, vol. 15, no. 5, pp. 677-685. https://doi.org/10.1021/tx0101088

Identification of tobacco-derived compounds in human pancreatic juice. / Prokopczyk, Bogdan; Hoffmann, Dietrich; Bologna, Matthew; Cunningham, A. John; Trushin, Neil; Akerkar, Shobha; Boyiri, Telih; Amin, Shantu; Desai, Dhimant; Colosimo, Stephen; Pittman, Brian; Leder, Gerhard; Ramadani, Marco; Henne-Bruns, Doris; Beger, Hans G.; El-Bayoumy, Karam.

In: Chemical Research in Toxicology, Vol. 15, No. 5, 30.05.2002, p. 677-685.

Research output: Contribution to journalArticle

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AU - Prokopczyk, Bogdan

AU - Hoffmann, Dietrich

AU - Bologna, Matthew

AU - Cunningham, A. John

AU - Trushin, Neil

AU - Akerkar, Shobha

AU - Boyiri, Telih

AU - Amin, Shantu

AU - Desai, Dhimant

AU - Colosimo, Stephen

AU - Pittman, Brian

AU - Leder, Gerhard

AU - Ramadani, Marco

AU - Henne-Bruns, Doris

AU - Beger, Hans G.

AU - El-Bayoumy, Karam

PY - 2002/5/30

Y1 - 2002/5/30

N2 - Cancer of the pancreas is the fourth leading cause of cancer mortality in the USA with an estimated 28 900 deaths in 2001. Several factors have been implicated in the etiology of this disease. However, at present, only cigarette smoking has been positively associated with pancreatic cancer. It is our working hypothesis that tobacco-derived compounds can be delivered to the pancreas where, upon metabolic activation, they can initiate carcinogenesis. Our current investigation was conducted to determine whether cotinine and tobacco-specific nitrosamines (TSNA) are present in human pancreatic juice. Smoking status was assessed by the determination of levels of urinary cotinine and was further supported by quantifying nicotine in hair. The TSNA were extracted from the pancreatic juice of 18 smokers and 9 nonsmokers by supercritical carbon dioxide that contained 10% methanol. The extracts were analyzed for TSNA, namely, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN), by gas chromatography with mass spectrometric detection using a selected ion monitoring technique (GC-SIM-MS). Twenty-three extracts of human pancreatic juice were also analyzed for the presence of the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by GC-SIM-MS and by gas chromatography interfaced wit a thermal energy analyzer (GC-TEA; TEA, a nitrosamine-specific detector). Cotinine was detected in all analyzed samples of pancreatic juice from smokers (129 ± 150 ng/mL juice; mean ± standard deviation) and was present in only two of the nine samples of pancreatic juice from nonsmokers. Its levels in these two samples were 7 and 9 ng/mL juice. NNK was detected in 15 of 18 samples (83%) from smokers at levels from 1.37 to 604 ng/mL pancreatic juice. In nine samples of pancreatic juice from nonsmokers, NNK ranged from not detected (in three samples) to 96.8 ng/mL juice. In pancreatic juice from smokers the mean level of NNK (88.7 ± 161 ng/mL juice) was significantly higher (p < 0.04) than in that from nonsmokers (12.4 ± 31.7 ng/mL juice). In addition to NNK, NNN was found in two samples of pancreatic juice of smokers at levels of 68.1 and 242 ng/mL juice; NNN was not detected in any other sample. NNAL was present in 8 of 14 pancreatic juice samples (57%) from smokers and in three of nine samples (33%) from nonsmokers. This research presents preliminary data that supports the hypothesis that pancreatic tissue is exposed to TSNA and that they may be important contributors to pancreatic carcinogenesis in humans.

AB - Cancer of the pancreas is the fourth leading cause of cancer mortality in the USA with an estimated 28 900 deaths in 2001. Several factors have been implicated in the etiology of this disease. However, at present, only cigarette smoking has been positively associated with pancreatic cancer. It is our working hypothesis that tobacco-derived compounds can be delivered to the pancreas where, upon metabolic activation, they can initiate carcinogenesis. Our current investigation was conducted to determine whether cotinine and tobacco-specific nitrosamines (TSNA) are present in human pancreatic juice. Smoking status was assessed by the determination of levels of urinary cotinine and was further supported by quantifying nicotine in hair. The TSNA were extracted from the pancreatic juice of 18 smokers and 9 nonsmokers by supercritical carbon dioxide that contained 10% methanol. The extracts were analyzed for TSNA, namely, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN), by gas chromatography with mass spectrometric detection using a selected ion monitoring technique (GC-SIM-MS). Twenty-three extracts of human pancreatic juice were also analyzed for the presence of the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by GC-SIM-MS and by gas chromatography interfaced wit a thermal energy analyzer (GC-TEA; TEA, a nitrosamine-specific detector). Cotinine was detected in all analyzed samples of pancreatic juice from smokers (129 ± 150 ng/mL juice; mean ± standard deviation) and was present in only two of the nine samples of pancreatic juice from nonsmokers. Its levels in these two samples were 7 and 9 ng/mL juice. NNK was detected in 15 of 18 samples (83%) from smokers at levels from 1.37 to 604 ng/mL pancreatic juice. In nine samples of pancreatic juice from nonsmokers, NNK ranged from not detected (in three samples) to 96.8 ng/mL juice. In pancreatic juice from smokers the mean level of NNK (88.7 ± 161 ng/mL juice) was significantly higher (p < 0.04) than in that from nonsmokers (12.4 ± 31.7 ng/mL juice). In addition to NNK, NNN was found in two samples of pancreatic juice of smokers at levels of 68.1 and 242 ng/mL juice; NNN was not detected in any other sample. NNAL was present in 8 of 14 pancreatic juice samples (57%) from smokers and in three of nine samples (33%) from nonsmokers. This research presents preliminary data that supports the hypothesis that pancreatic tissue is exposed to TSNA and that they may be important contributors to pancreatic carcinogenesis in humans.

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Prokopczyk B, Hoffmann D, Bologna M, Cunningham AJ, Trushin N, Akerkar S et al. Identification of tobacco-derived compounds in human pancreatic juice. Chemical Research in Toxicology. 2002 May 30;15(5):677-685. https://doi.org/10.1021/tx0101088