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Publications

Use of rodent data for cancer risk assessment of smokeless tobacco in the regulatory context

Nilsson, Robert

(2017)

TY  - JOUR
AU  - Nilsson, Robert
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1687
AB  - To support risk management decisions, information from different fields has been integrated in this presentation to provide a realistic quantitative cancer risk assessment of smokeless tobacco. Smoking among Swedish men is currently below 10%, while about 20% use a special smokeless tobacco (snus) as a substitute for cigarettes. Epidemiological data and molecular biomarkers demonstrate that rodent bioassays with tobacco specific nitrosamines (TSNA) overestimate cancer risk from snus by more than one order of magnitude. The underlying reasons are discussed. DNA damage constitutes a necessary, although not sufficient prerequisite for cancer initiation. Individuals who have not used tobacco exhibit DNA lesions identical with those induced by TSNA. No increase above this adduct background can be shown from snus, and extensive epidemiological studies in Sweden have failed to demonstrate elevated cancer risks even in long term users. A bench mark for acceptable risk of 1/10(6) derived from rodent data has been suggested when regulating snus. By relating similarly derived estimates for some food contaminants, the implementation even of a limit of 1/10(4) may be unrealistic. The management of smokeless tobacco products has rarely been based on a scientifically sound risk assessment, where attention is given to the outstandingly higher hazards associated with smoking. (C) 2017 Elsevier Inc. All rights reserved.
T2  - Regulatory Toxicology and Pharmacology
T1  - Use of rodent data for cancer risk assessment of smokeless tobacco in the regulatory context
VL  - 88
SP  - 338
EP  - 348
DO  - 10.1016/j.yrtph.2017.06.005
ER  - 
@article{
author = "Nilsson, Robert",
year = "2017",
abstract = "To support risk management decisions, information from different fields has been integrated in this presentation to provide a realistic quantitative cancer risk assessment of smokeless tobacco. Smoking among Swedish men is currently below 10%, while about 20% use a special smokeless tobacco (snus) as a substitute for cigarettes. Epidemiological data and molecular biomarkers demonstrate that rodent bioassays with tobacco specific nitrosamines (TSNA) overestimate cancer risk from snus by more than one order of magnitude. The underlying reasons are discussed. DNA damage constitutes a necessary, although not sufficient prerequisite for cancer initiation. Individuals who have not used tobacco exhibit DNA lesions identical with those induced by TSNA. No increase above this adduct background can be shown from snus, and extensive epidemiological studies in Sweden have failed to demonstrate elevated cancer risks even in long term users. A bench mark for acceptable risk of 1/10(6) derived from rodent data has been suggested when regulating snus. By relating similarly derived estimates for some food contaminants, the implementation even of a limit of 1/10(4) may be unrealistic. The management of smokeless tobacco products has rarely been based on a scientifically sound risk assessment, where attention is given to the outstandingly higher hazards associated with smoking. (C) 2017 Elsevier Inc. All rights reserved.",
journal = "Regulatory Toxicology and Pharmacology",
title = "Use of rodent data for cancer risk assessment of smokeless tobacco in the regulatory context",
volume = "88",
pages = "338-348",
doi = "10.1016/j.yrtph.2017.06.005"
}
Nilsson, R.. (2017). Use of rodent data for cancer risk assessment of smokeless tobacco in the regulatory context. in Regulatory Toxicology and Pharmacology, 88, 338-348.
https://doi.org/10.1016/j.yrtph.2017.06.005
Nilsson R. Use of rodent data for cancer risk assessment of smokeless tobacco in the regulatory context. in Regulatory Toxicology and Pharmacology. 2017;88:338-348.
doi:10.1016/j.yrtph.2017.06.005 .
Nilsson, Robert, "Use of rodent data for cancer risk assessment of smokeless tobacco in the regulatory context" in Regulatory Toxicology and Pharmacology, 88 (2017):338-348,
https://doi.org/10.1016/j.yrtph.2017.06.005 . .
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Cell Proliferation Assay - Method Optimisation for in Vivo Labeling of DNA in the Rat Forestomach

Joksić, Gordana; Mićić, Mileva; Filipović, Jelena G.; Drakulić, Dunja R.; Stanojlović, Miloš R.; Calija, Bojan; Valenta-Šobot, Ana; Demajo, Miroslav; Nilsson, Robert

(2017)

TY  - JOUR
AU  - Joksić, Gordana
AU  - Mićić, Mileva
AU  - Filipović, Jelena G.
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Calija, Bojan
AU  - Valenta-Šobot, Ana
AU  - Demajo, Miroslav
AU  - Nilsson, Robert
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1584
AB  - The study of cell proliferation is a useful tool in the fields of toxicology, pathophysiology and pharmacology. Cell proliferation and its degree can be evaluated using 5-bromo-2deoxyuridine which is incorporated into the newly synthesized DNA. The aim of this study was the optimization of subcutaneous application of 5-bromo-2-deoxyuridine implantation for continuous and persistent marking of proliferating cells in the rat forestomach. 3-tert-Butyl-4-hydroxyanisole was used as the agent that ensures cell proliferation. In order to determine the optimal dose for proliferating cells labeling, 5-bromo-2-deoxyuridine doses of 50 mg, 100 mg, 200 mg or 350 mg were implemented 2 days prior to sacrifice by flat-faced cylindrical matrices. Immunohistochemical analysis using 5-bromo-2-deoxyuridine in situ detection kit was performed for the detection of 5-bromo-2-deoxyuridine labeled cells. The results showed that for adult rats, the optimum 5-bromo-2-deoxyuridine dose is 200 mg per animal for subcutaneous application. The here described manner of 5-bromo-2-deoxyuridine in vivo labeling provides a simple, efficient, and reliable method for cell labeling, and at the same minimizes stress to animals.
T2  - Acta Veterinaria, Beograd
T1  - Cell Proliferation Assay - Method Optimisation for in Vivo Labeling of DNA in the Rat Forestomach
VL  - 67
IS  - 1
SP  - 1
EP  - 10
DO  - 10.1515/acve-2017-0001
ER  - 
@article{
author = "Joksić, Gordana and Mićić, Mileva and Filipović, Jelena G. and Drakulić, Dunja R. and Stanojlović, Miloš R. and Calija, Bojan and Valenta-Šobot, Ana and Demajo, Miroslav and Nilsson, Robert",
year = "2017",
abstract = "The study of cell proliferation is a useful tool in the fields of toxicology, pathophysiology and pharmacology. Cell proliferation and its degree can be evaluated using 5-bromo-2deoxyuridine which is incorporated into the newly synthesized DNA. The aim of this study was the optimization of subcutaneous application of 5-bromo-2-deoxyuridine implantation for continuous and persistent marking of proliferating cells in the rat forestomach. 3-tert-Butyl-4-hydroxyanisole was used as the agent that ensures cell proliferation. In order to determine the optimal dose for proliferating cells labeling, 5-bromo-2-deoxyuridine doses of 50 mg, 100 mg, 200 mg or 350 mg were implemented 2 days prior to sacrifice by flat-faced cylindrical matrices. Immunohistochemical analysis using 5-bromo-2-deoxyuridine in situ detection kit was performed for the detection of 5-bromo-2-deoxyuridine labeled cells. The results showed that for adult rats, the optimum 5-bromo-2-deoxyuridine dose is 200 mg per animal for subcutaneous application. The here described manner of 5-bromo-2-deoxyuridine in vivo labeling provides a simple, efficient, and reliable method for cell labeling, and at the same minimizes stress to animals.",
journal = "Acta Veterinaria, Beograd",
title = "Cell Proliferation Assay - Method Optimisation for in Vivo Labeling of DNA in the Rat Forestomach",
volume = "67",
number = "1",
pages = "1-10",
doi = "10.1515/acve-2017-0001"
}
Joksić, G., Mićić, M., Filipović, J. G., Drakulić, D. R., Stanojlović, M. R., Calija, B., Valenta-Šobot, A., Demajo, M.,& Nilsson, R.. (2017). Cell Proliferation Assay - Method Optimisation for in Vivo Labeling of DNA in the Rat Forestomach. in Acta Veterinaria, Beograd, 67(1), 1-10.
https://doi.org/10.1515/acve-2017-0001
Joksić G, Mićić M, Filipović JG, Drakulić DR, Stanojlović MR, Calija B, Valenta-Šobot A, Demajo M, Nilsson R. Cell Proliferation Assay - Method Optimisation for in Vivo Labeling of DNA in the Rat Forestomach. in Acta Veterinaria, Beograd. 2017;67(1):1-10.
doi:10.1515/acve-2017-0001 .
Joksić, Gordana, Mićić, Mileva, Filipović, Jelena G., Drakulić, Dunja R., Stanojlović, Miloš R., Calija, Bojan, Valenta-Šobot, Ana, Demajo, Miroslav, Nilsson, Robert, "Cell Proliferation Assay - Method Optimisation for in Vivo Labeling of DNA in the Rat Forestomach" in Acta Veterinaria, Beograd, 67, no. 1 (2017):1-10,
https://doi.org/10.1515/acve-2017-0001 . .
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Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)

Nilsson, Robert; Mićić, Mileva; Filipović, Jelena G.; Valenta-Šobot, Ana; Drakulić, Dunja R.; Stanojlović, Miloš R.; Joksić, Gordana

(Elsevier, 2016)

TY  - JOUR
AU  - Nilsson, Robert
AU  - Mićić, Mileva
AU  - Filipović, Jelena G.
AU  - Valenta-Šobot, Ana
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Joksić, Gordana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1058
AB  - The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco (snus), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity. The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine. After 6 weeks exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity. (C) 2016 Elsevier Inc. All rights reserved.
PB  - Elsevier
T2  - Regulatory Toxicology and Pharmacology
T1  - Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)
VL  - 76
SP  - 94
EP  - 101
DO  - 10.1016/j.yrtph.2016.01.017
ER  - 
@article{
author = "Nilsson, Robert and Mićić, Mileva and Filipović, Jelena G. and Valenta-Šobot, Ana and Drakulić, Dunja R. and Stanojlović, Miloš R. and Joksić, Gordana",
year = "2016",
abstract = "The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco (snus), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity. The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine. After 6 weeks exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity. (C) 2016 Elsevier Inc. All rights reserved.",
publisher = "Elsevier",
journal = "Regulatory Toxicology and Pharmacology",
title = "Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)",
volume = "76",
pages = "94-101",
doi = "10.1016/j.yrtph.2016.01.017"
}
Nilsson, R., Mićić, M., Filipović, J. G., Valenta-Šobot, A., Drakulić, D. R., Stanojlović, M. R.,& Joksić, G.. (2016). Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus). in Regulatory Toxicology and Pharmacology
Elsevier., 76, 94-101.
https://doi.org/10.1016/j.yrtph.2016.01.017
Nilsson R, Mićić M, Filipović JG, Valenta-Šobot A, Drakulić DR, Stanojlović MR, Joksić G. Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus). in Regulatory Toxicology and Pharmacology. 2016;76:94-101.
doi:10.1016/j.yrtph.2016.01.017 .
Nilsson, Robert, Mićić, Mileva, Filipović, Jelena G., Valenta-Šobot, Ana, Drakulić, Dunja R., Stanojlović, Miloš R., Joksić, Gordana, "Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)" in Regulatory Toxicology and Pharmacology, 76 (2016):94-101,
https://doi.org/10.1016/j.yrtph.2016.01.017 . .
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