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Biomedical subjects

K D Brunnemann

Publications and source records attributed to K D Brunnemann.

At least 37 records · Page 2Linked to original sources
PubMed1991

Assessment of major carcinogens and alkaloids in the tobacco and mainstream smoke of USSR cigarettes.

Tobacco and mainstream smoke of USSR cigarettes were analyzed for carcinogens. The pH values of suspensions of the tobacco (5.4-5.6) and the nitrate content of the tobaccos (0.4-1.7%) were as expected for flue-cured and sun-cured tobaccos and mixtures thereof. The nicotine levels of the cigarette tobaccos (0.76-0.94%) and total alkaloid content (0.85-1.08%) were relatively low compared with tobaccos used in Western European and US cigarettes. The concentrations of tobacco-specific N-nitrosamines in the cigarette tobaccos were also low (N'-nitrosonornicotine 0.36-0.85 microgram/g) compared with those in bright, oriental and blended cigarette tobaccos in Western countries (0.3-19 microgram/g). The 2 non-filter and 4 filter cigarettes from the USSR had slow burning rates and yielded 14.0-16.7 puffs/cigarette, while puff yields for commercial cigarettes in Western countries average less than or equal to 11 puffs/cigarette. Consequently, tar and benzo(a)pyrene yields in the smoke of all cigarettes as well as nitrosamine yields were high, especially in the smoke of the filter cigarettes. It appears that an increase in the burning rates of these cigarettes should lead to lower smoke yields.

Alkaloids↗
PubMed1991

Composition of popular tobacco products in Thailand, and its relevance to disease prevention.

BACKGROUND: This report presents new findings on the composition of the three best-selling brands of commercially produced Thai cigarettes, representing about 80% of market share in Thailand, and six best-selling tobacco products, including hand-rolled cigarettes and cigars. RESULTS: With one exception, all Thai cigarettes yielded higher levels of tar and nicotine than U.S. brands sold in Thailand. High levels of tar, nicotine, and carbon monoxide (CO) were found in the smoke of popular Thai cigars (Khiyo) and Burmese cigars sold in Thailand. All tobacco products tested were ranked in order of smoke yields of tar (cigarettes, 4.5 to 40.8 mg/cigarette), nicotine (0.19 to 5.77 mg/cigarette), and CO (3.1 to 9.5 mg/cigarette). The labels "very strong," "strong," and "mild," used in rating the tobacco quality by the growers in Thailand, were not found to reflect the relative nicotine and tar yields. From 1985-1990, per capita consumption of cigarettes in Thailand increased 1.4-fold. CONCLUSION: This report provides information that may prove helpful in the evaluation of the tar, nicotine, and carbon monoxide yields of cigarettes and cigars in Thailand compared with levels in U.S. cigarettes. It is our goal to offer the scientific basis for voluntary and/or regulated reduction of the smoke yields of tobacco products in Thailand.

Advertising↗
PubMed1991

New brands of oral snuff.

Snuff dipping is causally related to cancer of the oral cavity and pharynx. The most powerful carcinogens in snuff are nitroso compounds, particularly the tobacco-specific N-nitrosamines (TSNA). Concentrations of TSNA in snuff exceed the known concentrations of carcinogenic nitrosamines in any other consumer product by two to three orders of magnitude. During the last decade a gradual decrease in TSNA has occurred in the two leading snuff brands in the USA (about 90% of the market). Of two recently introduced snuff brands one has relatively low levels of nitroso compounds while the other contains the highest concentrations of nitrosamines ever reported in smokeless tobacco. This observation suggests that control of nitrosamines in snuff brands on the US market is desirable.

Alkaloids↗
PubMed1991

Analytical studies on tobacco-specific N-nitrosamines in tobacco and tobacco smoke.

Chemical-analytical studies have led to the identification of approximately 3000 compounds in tobacco and 4000 in tobacco smoke. These include carcinogens in processed tobacco as well as tumor initiators, tumor promoters, cocarcinogens, and organ-specific carcinogens in tobacco smoke. The latter group includes N-nitrosamines, in particular those that derive from nicotine and other tobacco alkaloids, the TSNA. In vitro nitrosation of nicotine yields NNN, NNA, and NNK. Nitrosation of other tobacco alkaloids leads to the formation of NAT, and NAB. Our analytical studies using GC-TEA have led to the identification of seven TSNA in tobacco and tobacco smoke. In addition to NNN, NAT, NAB, and NNK, we also identified NNAL, iso-NNAL, and, most recently, iso-NNAC. Their levels range from 0.01 to 92 ppm in tobacco and from 6 to 530 ng/cigarette in tobacco smoke. The high levels observed in snuff are primarily due to fermentation and aging. Technological methods exist today to reduce the levels of TSNA in both tobacco and cigarette smoke.

Animals↗
PubMed1991

Analysis and pyrolysis of some N-nitrosamino acids in tobacco and tobacco smoke.

A new tobacco-specific nitrosamine, 4-(N-nitrosomethylamino)-4-(3-pyridyl)butyric acid (iso-NNAC), has been identified in tobacco, and its structure was confirmed by gas chromatography-mass spectrometry following enrichment of a tobacco extract. The levels of iso-NNAC ranged from 0.01 to 0.95 ppm. It does not induce DNA repair in primary rat hepatocytes and is inactive as a tumorigenic agent in strain A mice. In order to study the fate of nitrosamino acids during smoking, we spiked cigarettes with the following N-nitrosamino acids: iso-NNAC, 3-(nitrosomethylamino)propionic acid (NMPA), 4-(nitrosomethylamino)butyric acid (NMBA), N-nitrososarcosine (NSAR) and N-nitrosoproline (NPRO). NMPA and NMBA were partially transferred, unchanged, during smoking and partially formed the corresponding methyl esters, while pyrolysis of NSAR and NPRO resulted mainly in their decarboxylating products. This is the first time that the pyrosynthesis of methyl esters has been observed during smoking.

Animals↗
PubMed1991

Studies in tobacco carcinogenesis.

The vapour phase of freshly generated cigarette mainstream smoke, of sidestream smoke and of environmental tobacco smoke was analysed for such tumorigenic agents as benzene, 1,3-butadiene and acrolein with a newly developed, highly sensitive gas chromatography-mass selective detection method. The major carcinogen in tobacco smoke, catechol, was studied in regard to its specific action on the metabolism of benzo[a]pyrene in mouse lung and mouse skin. The major tobacco-specific carcinogens in tobacco and its smoke are the nicotine-derived N-nitrosamines, N'-nitrosonornicotine and 4-(nitroso-methylamino)-1-(3-pyridyl)-1-butanone. A third nitrosamine that can be formed in vitro by nitrosation of nicotine is 1-(nitrosomethylamino)-1-(3-pyridyl)butylaldehyde. This aldehyde is not present in tobacco products, but its noncarcinogenic oxidation product, 4-(nitrosomethylamino)-1-(3-pyridyl)butyric acid, was found in tobacco and can be formed from the major nicotine metabolite, cotinine. It is also likely that this acid can be formed by endogenous reactions.

Animals↗
PubMed1991

Carcinogenic substances in Soviet tobacco products.

Chemical carcinogens were determined in mainstream smoke from nonfilter cigarettes produced and consumed in the USSR and in nass, a mixture of tobacco, lime, ash and cotton oil. Cigarettes contained high levels of tar (23-25 mg/cigarette) and nicotine (1.5-1.9 mg/cigarette) and, generally, a high content of polycyclic aromatic hydrocarbons, which are major epithelial carcinogens, N-nitrosamines, which are organ-specific carcinogens, and some carcinogenic metals, such as arsenic and chromium. Nass contained the tobacco-specific N-nitroso compounds, N'-nitrosonornicotine, N'-nitrosoanatabine, N'-nitrosoanabasine and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone, as well as volatile N-nitrosamines, but at levels lower than in other types of chewing tobacco and snuff. The low levels in nass are due to the short ageing process used, in contrast to commercially produced chewing tobacco and fine-cut snuff, which are highly processed products requiring long ageing and fermentation.

Carcinogens↗
PubMed1990

Analysis of 1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection.

An analytical procedure was developed for the analysis of 1,3-butadiene, acrolein, isoprene, benzene and toluene in the gas phase of cigarette smoke and environmental tobacco smoke (ETS) utilizing cryogenic gas chromatography-mass selective detection (GC-MSD). The MSD was operated in the selective ion monitoring (SIM) mode. The compounds of interest eluted in less than 15 min. The gas phase of freshly generated mainstream smoke was introduced into the GC-MSD via a 10-port gas sampling valve on a puff-by-puff basis. This method minimizes the ageing of tobacco smoke. The levels of 1,3-butadiene in the mainstream smoke ranged from 16 to 75 micrograms/cigarette. The gas phase of sidestream smoke was trapped in methanol using three midget impingers at -78 degrees C. The amount of 1,3-butadiene in the sidestream smoke ranged from 205-361 micrograms/cigarette. The concentration of 1,3-butadiene in ETS in a smoke-filled bar amounted to 2.7-4.5 micrograms/m3.

Acrolein↗
PubMed1990

"Tar", nicotine, and carbon monoxide content of Thai cigarettes, and implications for cancer prevention in Thailand.

This report presents new findings on the very high contents of nicotine (i.e., 1.64 to 5.77 mg) and "tar" (i.e., 21.3 to 28.1 mg) in major brands of commercially produced Thai cigarettes and local tobacco used for rolled cigarettes. These nicotine levels are relevant to the addictive properties of Thai cigarettes, while the "tar" levels are related to risk of cancer of the lung and other sites. Consumption of tobacco products nearly tripled over the last 2 decades (1966 to 1987). The relative frequency of lung cancer in Thailand in 1982 was high in both urban and rural areas, with geographic differences particularly for females, and increased from 1975 to 1982 in both males and females. The important implications of cigarette contents and consumption are presented in relation to future cancer patterns and cancer prevention in Thailand. Labeling of cigarettes, in terms of "tar" and nicotine contents is needed along with educational programs dealing with the harmful and addictive effects of these substances.

Carbon Monoxide↗
PubMed1990

Smokeless tobacco: a product for the new generation of tobacco users. Dipping and chewing in the Northwest Territories, Canada, and its global relevance.

The use of smokeless tobacco appears to be a socially acceptable behavior among certain ethnic and cultural groups in developing and developed countries. Some native groups in the Northwest Territories have traditionally used smokeless tobacco. With the visits of the merchant supply ships to the Northwest Territories in the early 1950's, a wider commercial variety of smokeless tobacco began to be used. Of great concern is the generation of Canadian children and adolescents who start this habit and become addicted to smokeless tobacco during their primary and secondary school years. Smokeless tobacco is reemerging as a popular form of tobacco among children and adolescents in Canada, the United States (including Alaska), Scandinavia and Britain. Chemical analysis of samples of smokeless tobacco from six countries has revealed that moist snuff obtained in 1985, from Gjoa Haven, Northwest Territories (imported from the United States) had the highest levels of cancer causing tobacco-specific nitrosamines (TSNA) of 228,400 and 240,100 parts per billion. If these levels were found in any other consumer product today, it would be banned from the marketplace. Because of their known carcinogenicity, the United States Department of Agriculture and Federal Food and Drug Administration have set up strict tolerance levels for human exposure to these chemicals and they prohibit the sale of beer, bacon or baby bottle nipples that contain levels greater than 10 parts per billion. TSNA concentrations in snuff exceed the levels of nitrosamines in other consumer products by over one hundredfold. During snuff dipping or chewing tobacco, the nitrosation process continues within the mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Chemopreventive trials with vitamin A and beta-carotene: some unresolved issues.

The administration of beta-carotene (180 mg/week) plus vitamin A (100,000 IU/week) or vitamin A alone (200,000 IU/week) to chewers of betel quids in Kerala, India led to a reduction in the frequency of micronucleated buccal mucosal cells, a remission of oral leukoplakia, and an inhibition of the development of new leukoplakias. The advantages of this test system include a profound knowledge of exposure levels to tobacco-specific nitrosamines, areca nut-specific nitrosamines, and reactive oxygen species (ROS)-generating polyphenolics; the ease of quantitating micronuclei in exfoliated buccal mucosal cells and oral leukoplakia by noninvasive procedures; and solid information on the incidence of preneoplastic lesions and carcinomas. Some practical issues such as the level of nontoxic beta-carotene which could maintain the reduced frequency of micronucleated cells and the remission of oral leukoplakias for prolonged periods of time, the logistics of distributing beta-carotene to the many millions of smokeless tobacco users who are at elevated risk for oral cancer, and the possibility of using beta-carotene in the form of sweet potatoes or red palm oil, which could contain an economical source of beta-carotene for developing countries in which most of the tobacco chewers live, still remain unresolved.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Determination of benzene, toluene and 1,3-butadiene in cigarette smoke by GC-MDS.

An analytical procedure was devised for the determination of selected gas phase constituents in cigarette smoke utilizing capillary gas chromatography and mass selective detection (GC-MSD); the MSD was used in the selective ion monitoring mode (SIM). The gas of freshly generated mainstream smoke was analyzed via a 10-port gas sampling valve on a puff-by-puff basis. Benzene, toluene, and 1,3-butadiene were found in the range of 6-73, 5-88, and 16-75 micrograms/cigarette, respectively. The gas phase of sidestream smoke was trapped in methanol using 3 midget impingers at -78 degrees C. Benzene in sidestream smoke was found in the range of 490-840 micrograms/cigarette; toluene and 1,3-butadiene levels were 1,090-1,690 and 300-470 micrograms/cigarette, respectively. Environmental tobacco smoke (ETS), sampled in a smoke-filled bar, was analyzed using the cold trap method. The concentrations of benzene and toluene in this indoor air were found to be 26-36 and 41-80 micrograms/m3, respectively, while 1,3-butadiene was present at 3.3-4.5 micrograms/m3.

Benzene↗
PubMed1989

Identification and analysis of a nicotine-derived N-nitrosamino acid and other nitrosamino acids in tobacco.

Research on carcinogenic, tobacco-specific N-nitrosamines (TSNA) led to the identification and analysis of 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid (iso-NNAC) in tobacco and tobacco smoke. In order to isolate iso-NNAC, an aqueous tobacco extract at pH 4 was partitioned with ethyl acetate after the other N-nitrosamino acids and TSNA were removed at pH 2 and pH 9 respectively. The structure of iso-NNAC was confirmed by GC-MS after enrichment of the methylated pH 4 fraction by chromatography on an alumina column. Iso-NNAC, 3-(methylnitrosamino)propionic acid, 4-(methylnitrosamino)butyric acid, N-nitrosoproline and TSNA were determined by GC-TEA in various smokeless tobaccos as well as in reference cigarettes. The levels of iso-NNAC in tobacco products ranged from 0.01 p.p.m. in chewing tobacco to 0.95 p.p.m. in dry snuff. The transfer rate of unchanged iso-NNAC into the mainstream smoke of a non-filter cigarette amounted to 0.85%. Iso-NNAC does not induce DNA repair in primary rat hepatocytes and is inactive as a tumorigenic agent in strain A mice.

Carcinogens↗
PubMed1987

3-(Methylnitrosamino)propionitrile: occurrence in saliva of betel quid chewers, carcinogenicity, and DNA methylation in F344 rats.

3-(Methylnitrosamino)propionitrile (MNPN), a potent carcinogen in F344 rats, was detected for the first time in the saliva of betel quid chewers at levels ranging from 0.5 to 11.4 micrograms/liter. The tumorigenic properties of MNPN and its potential to methylate DNA in F344 rats were evaluated. Groups of 21 male and 21 female rats were given 60 s.c. injections over a 20-week period (total doses 0.055 and 0.23 mmol per rat). The experiment was terminated after 106 weeks. MNPN at the higher dose induced 18 (86%) malignant tumors of the nasal cavity in male and 15 (71%) in female rats. The lower dose induced nine (43%) liver tumors. Groups of four or five male F344 rats were treated with a single s.c. or i.v. injection of MNPN (0.4 mmol/kg). MNPN was also administered to rats by swabbing the oral cavity (2.21 mmol/kg). The levels of 7-methylguanine and O6-methylguanine, formed 0.5-36 h after treatment, were measured in the liver, nasal mucosa, esophagus, and oral issues. The highest levels of methylated guanines were detected in the nasal cavity independent of the route of administration. The results of this study demonstrate that MNPN is present in the saliva of betel quid chewers and is a potent carcinogen in F344 rats.

Adult↗
PubMed1987

Tobacco-specific nitrosamines in the saliva of Inuit snuff dippers in the Northwest Territories of Canada.

Levels of tobacco-specific nitrosamines (TSNA), nicotine and cotinine were estimated in the saliva of 20 snuff dippers (Inuit, Northwest Territories, Canada). Levels of N'-nitrosonornicotine (NNN), 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosoanatabine (NAT) plus N-nitrosoanabiasine (NAB) found in the saliva following a 15-min period of keeping 0.5-1.5 g of moist snuff in the gingival groove are considerable: 115-2610 ppb NNN, 123-4560 ppb NAT + NAB, and up to 201 ppb NNK. The amount of TSNA in the saliva increases with the length of time that the snuff is kept in the mouth. The estimated total amount of 444 micrograms TSNA, the largest part of which will be swallowed, exceeds by far the amounts of nitrosamines ingested through drinking beer (0.34 micrograms/day), eating cured meat products (0.17 micrograms/day), or using cosmetics (0.41 micrograms/day). The relatively high levels of potentially carcinogenic TSNA in the saliva, together with the current popularity of snuff usage by teenagers, is of particular concern.

Canada↗
PubMed1987

A critical look at N-nitrosamines in environmental tobacco smoke.

The amounts of cigarette smoke carcinogens released into the environment as sidestream smoke (SS) constituents are generally twice as high as the levels of the carcinogens that are inhaled as mainstream smoke (MS). However, certain carcinogens in undiluted SS, such as nitrosamines, exceed MS levels up to 50 times. Regardless of the fact that SS is usually substantially diluted before being inhaled, its constituents can be determined in environmental tobacco smoke (ETS) by modern analytical methods and levels of exposure of involuntary smokers can be assessed by the use of specific markers. Currently, the uptake of ETS by nonsmokers is determined by measuring nicotine and its metabolite cotinine in saliva, serum and/or urine. In on-going studies, we are now exploring the determination of the two highly carcinogenic nicotine-derived nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively of their metabolites, in physiological fluids of smokers and nonsmokers.

Animals↗