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Mirjana V. Djordjevic

Other affiliations: Dana Corporation
Bio: Mirjana V. Djordjevic is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Tobacco smoke & Sidestream smoke. The author has an hindex of 33, co-authored 51 publications receiving 5618 citations. Previous affiliations of Mirjana V. Djordjevic include Dana Corporation.


Papers
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Journal ArticleDOI
TL;DR: The product changes, the smokers' dependence on nicotine which governs their smoking patterns, and the modified smoke chemistry support the hypothesis that differences in PAH and TSNA exposure may be linked to the observed different incidences of squamous cell cancer and adenocarcinoma of the lung.

439 citations

Journal ArticleDOI
TL;DR: Evidence is presented that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increase risk of lung cancer, especially pulmonary adenocarcinoma, in smokers.
Abstract: Nicotine and the minor tobacco alkaloids give rise to tobacco-specific N-nitrosamines (TSNA) during tobacco processing and during smoking. Chemical-analytical studies led to the identification of seven TSNA in smokeless tobacco (< or = 25 micrograms/g) and in mainstream smoke of cigarettes (1.3 micrograms TSNA/cigarette). Indoor air polluted by tobacco smoke may contain up to 24 pg/L of TSNA. In mice, rats, and hamsters, three TSNA, N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are powerful carcinogens; two TSNA are moderately active as carcinogens; and two TSNA appear not to be carcinogenic. The TSNA are procarcinogens, agents that require metabolic activation. The active forms of the carcinogenic TSNA react with cellular components, including DNA, and with hemoglobin (Hb). The Hb adducts in chewers and smokers serve as biomarkers for the uptake and metabolic activation of carcinogenic TSNA and the urinary excretion of NNAL as free alcohol and as glucuronide for the uptake of TSNA. The review presents evidence that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increased risk of lung cancer, especially pulmonary adenocarcinoma, in smokers. The high incidence of cancer of the upper digestive tract especially among men on the Indian subcontinent has been causally associated with chewing of betel quid mixed with tobacco. In addition to the TSNA, the betel quid chewers are exposed to four N-nitrosamines that are formed during chewing from the Areca alkaloids, two of these N-nitrosamines are carcinogens. The article also reviews approaches toward the reduction of the carcinogenic potency of smokeless tobacco, betel quid-tobacco mixtures, and cigarette smoke. Although the safest way to reduce the risk for tobacco-related cancers is to refrain from chewing and smoking, modifications of smokeless tobacco and of cigarettes are indicated to lead to less toxic products. Another more recent approach for reducing the carcinogenic effect of tobacco products is the application of chemopreventive agents, primarily of micronutrients. Future aspects in tobacco carcinogenesis, especially as it relates to TSNA, are expected in the field of molecular biochemistry and in biomarker studies, with the goal of identifying those tobacco and betel quid chewers and tobacco smokers who are at especially high risk for cancer.

362 citations

01 Jan 2000
TL;DR: The FTC protocol underestimates nicotine and carcinogen doses to smokers and overestimates the proportional benefit of low-yield cigarettes, so FTC-based nicotine medication doses prescribed/recommended for smoking cessation may need to be reassessed.
Abstract: Background: Cigarette smoke yields of tar and nicotine obtained under the Federal Trade Commission (FTC)-specified machine-smoking protocol (35-mL puff volume drawn for 2 seconds once per minute) may not accurately reflect the delivery of toxins and carcinogens to the smoker. We conducted this study to obtain more realistic estimates of exposure to components of cigarette smoke that affect lung cancer risk. Methods: We used a pressure transducer system to evaluate puffing characteristics for 133 smokers of cigarettes rated by the FTC at 1.2 mg of nicotine or less (56 smokers of low-yield cigarettes [<0.8 mg of nicotine per cigarette] and 77 smokers of medium-yield cigarettes [0.9‐ 1.2 mg of nicotine per cigarette]). We programmed measurements from a randomly chosen subset of 72 of these smokers into a piston-type machine to generate smoke from each smoker’s usual brand of cigarettes for assays of nicotine, carbon monoxide, tar, and the lung cancer-causing agents 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene. The FTC protocol was also used to assess levels of targeted components in the 11 brands most frequently smoked by study subjects. Results: Compared with the FTC protocol values, smokers of low- and medium-yield brands took in statistically significantly larger puffs (48.6 and 44.1 mL, respectively) at statistically significantly shorter intervals (21.3 and 18.5 seconds, respectively), and they drew larger total smoke volumes than specified in the FTC parameters. They received, respectively, 2.5 and 2.2 times more nicotine and 2.6 and 1.9 times more tar than FTC-derived amounts, as well as about twofold higher levels of benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Smokers of medium-yield cigarettes compared with smokers of low-yield cigarettes received higher doses of all components. Conclusions: The FTC protocol underestimates nicotine and carcinogen doses to smokers and overestimates the proportional benefit of low-yield cigarettes. Thus, FTCbased nicotine medication doses prescribed/recommended for smoking cessation may need to be reassessed. [J Natl Cancer Inst 2000;92:106‐11]

262 citations

Journal ArticleDOI
TL;DR: In this paper, the authors used a pressure transducer system to evaluate puffing characteristics for 133 smokers of cigarettes rated by the FTC at 1.2 mg of nicotine or less.
Abstract: Background: Cigarette smoke yields of tar and nicotine obtained under the Federal Trade Commission (FTC)-specified machine-smoking protocol (35-mL puff volume drawn for 2 seconds once per minute) may not accurately reflect the delivery of toxins and carcinogens to the smoker. We conducted this study to obtain more realistic estimates of exposure to components of cigarette smoke that affect lung cancer risk. Methods: We used a pressure transducer system to evaluate puffing characteristics for 133 smokers of cigarettes rated by the FTC at 1.2 mg of nicotine or less (56 smokers of low-yield cigarettes [

253 citations


Cited by
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Journal ArticleDOI
TL;DR: Up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe.

4,722 citations

Journal ArticleDOI
TL;DR: Assessment of the strength of associations between BMI and different sites of cancer and differences in these associations between sex and ethnic groups should inform the exploration of biological mechanisms that link obesity with cancer.

4,504 citations

Journal ArticleDOI
TL;DR: The total number of new cases of cancer in Europe appears to have increased by 300,000 since 2004 and the ageing of the European population will cause these numbers to continue to increase even if age-specific rates remain constant.

4,155 citations

Journal ArticleDOI
TL;DR: Changing global incidence and mortality patterns for select common cancers and the opportunities for cancer prevention in developing countries are described.
Abstract: While incidence and mortality rates for most cancers (including lung, colorectum, female breast, and prostate) are decreasing in the United States and many other western countries, they are increasing in several less developed and economically transitioning countries because of adoption of unhealthy western lifestyles such as smoking and physical inactivity and consumption of calorie-dense food. Indeed, the rates for lung and colon cancers in a few of these countries have already surpassed those in the United States and other western countries. Most developing countries also continue to be disproportionately affected by cancers related to infectious agents, such as cervix, liver, and stomach cancers. The proportion of new cancer cases diagnosed in less developed countries is projected to increase from about 56% of the world total in 2008 to more than 60% in 2030 because of the increasing trends in cancer rates and expected increases in life expectancy and growth of the population. In this review, we describe these changing global incidence and mortality patterns for select common cancers and the opportunities for cancer prevention in developing countries.

2,577 citations

Journal ArticleDOI
TL;DR: By focusing in this review on several important carcinogens in tobacco smoke, the complexities in understanding tobacco-induced cancer can be reduced, and new approaches for lung cancer prevention can be envisioned.
Abstract: The complexity of tobacco smoke leads to some confusion about the mechanisms by which it causes lung cancer. Among the multiple components of tobacco smoke, 20 carcinogens convincingly cause lung tumors in laboratory animals or humans and are, therefore, likely to be involved in lung cancer induction. Of these, polycyclic aromatic hydrocarbons and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone are likely to play major roles. This review focuses on carcinogens in tobacco smoke as a means of simplifying and clarifying the relevant information that provides a mechanistic framework linking nicotine addiction with lung cancer through exposure to such compounds. Included is a discussion of the mechanisms by which tobacco smoke carcinogens interact with DNA and cause genetic changes--mechanisms that are reasonably well understood--and the less well defined relationship between exposure to specific tobacco smoke carcinogens and mutations in oncogenes and tumor suppressor genes. Molecular epidemiologic studies of gene-carcinogen interactions and lung cancer--an approach that has not yet reached its full potential--are also discussed, as are inhalation studies of tobacco smoke in laboratory animals and the potential role of free radicals and oxidative damage in tobacco-associated carcinogenesis. By focusing in this review on several important carcinogens in tobacco smoke, the complexities in understanding tobacco-induced cancer can be reduced, and new approaches for lung cancer prevention can be envisioned.

1,868 citations