Search PubMed⌕ Search

Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 397 records · Page 22Linked to original sources

Chemical studies on tobacco smoke. XLII. Nitrosonornicotine: presence in tobacco, formation and carcinogenicity.

NNN is the first organic carcinogen isolated from unburned tobacco. It has been found in smoking tobaccos, chewing tobaccos and in snuff in concentrations between 0.3 and 90.0 mug. This appears to be an unusually high concentration for a nitrosamine in an environmental agent. We have presented data which suggest that NNN, and possibly other unknown nitrosamines, are formed during the curing of tobacco and that the nitrate content of tobacco is an important factor in nitrosamine formation. Studies with N'-methylanabasine applied to tobacco plants are currently under way to test the idea that nicotine rather than nornicotine is the major precursor of NNN in processed tobacco. In mice, NNN induces adenomas of the lung. Bioassays with rats have shown that NNN is carcinogenic to the oesophagus and the nasal cavity. These chemical and biological data are consistent with the observation that tobacco chewers face an increased risk of cancer of the oesophagus. This observation does not, of course, rule out the possibility that other tobacco carcinogens are responsible for the increased cancer risk of tobacco chewers.

Animals↗

Tobacco and tobacco smoke.

Epidemiologic studies have demonstrated a causal relation between smoking of cigarettes and cancer of the lung in man. Women smokers, cigar, and pipe smokers also face an increased risk for lung cancer. Prospective and retrospective studies have found a correlation between smoking of cigarettes, cigars, and pipes and cancer of the oral cavity, larynx, and esophagus and for cigarette smokers increased risks to develop cancer of the pancreas, kidney, and urinary bladder. Dose responses have been established between number of cigarettes smoked and cancer of the respiratory and upper digestive tract. Tobacco chewers face an increased risk for cancer of the mouth and esophagus. Tobacco smoke has induced tumors of the lung in the dogs and of the larynx of hamsters. The particulate matter of the smoke is carcinogenic to the skin of mice and rabbits, and the bronchi and connective tissue of rats. In tobacco smoke were identified tumor initiators, tumor promoters, cocarcinogens and organ specific carcinogens. Chewing tobacco is a tumor promoting agent and contains traces of tobacco specific and carcinogenic nitrosamines. Ten to 15 yr after giving up smoking the ex-smoker faces the same low risk to develop cancer of the upper digestive tract, the lung, the pancreas, and the urinary tract as the nonsmoker. It should be our goal, therefore, to prevent young people from starting the smoking habit and to convince the smoker to quit smoking. So far, we can report no success in terms of decreasing smoking habits among younger people. On the other hand, we can take satisfaction from the fact that antismoking propaganda has had an effect on college educated males, that among the population as a whole, there is a considerable number of exsmokers; that smoking cessation clinics do prove cost effective and if they were to become part of every health care center, they could help a large number of heavy smokers who cannot seem to stop smoking on their own. We can also report that there has been a significant reduction in the tar yield of American cigarettes, a reduction which we hope will continue; that the tumorigenic activity of tobacco as measured in animal studies, has decreased; and that as a consequence of the above, the risk of lung cancer and other tobacco-related cancers among smokers of these cigarettes is lower than in years past. It is unlikely that man will ever be able to inhale smoke components as harmless as unpolluted air, but as long as we have a society which accepts this habit and as long as people find satisfaction in smoking, we must work towards the day when tobacco-related cancers and other diseases will be reduced to a minimum. With the world wide coperation of the scientific community, the Departments of Agriculture, and the tobacco industry, it is our hope that this goal will be achieved.

Age Factors↗

Improved rapid method to check electrode localizations in the brain.

A modification of known rapid methods to check electrode localization in the brain is described: the essential point consists in immersing the brain, after fixation in 4 percent Formalin, in pure heptane at -30 degrees C for 5 hr. Unstained sections, cut with the freezing microtome, are placed uncovered on glass slides and photographed (in an enlarger, as if they were negatives) either wet, to obtain a contrast resembling Weil staining, or dry, to obtain a picture corresponding to Nissl staining.

Animals↗

Chemical studies on tobacco smoke. XXXIII. N' -nitrosonornicotine in tobacco: analysis of possible contributing factors and biologic implications.

A chemical analytic method to determine N'-nitrosonornicotine (NNN) and N' -nitrosoanabasine (NAB) in tobacco was developed. NNN was found in the unburned tobacco of commercial products at concentrations betweeen 0.3 and 88.6 mug/g. The highest levels were observed in highly fermented snuff (29.1 mug/g) and fine-cut chewing tobacco (88.6 mug/g). NAB was not detected (smaller than 0.5 ng/g) in any tobacco examined. Two new tobacco components, N' -carbomethoxynornicotine and N' -carbomethoxyanabasine,were found. Possible origins of NNN in tobacco were discussed, especially in relation to concentrations of nitrite, nitate, and alkaloids, and in relation to pH and curing. Biologic implications, including the possible function of NNN (the first organic carcinogen isolated from unburned tobacco) as a causative factor in cancer of the oral cavity in tobacco chewers and betel quid chewers, were also discussed.

Alkaloids↗

A study of tobacco carcinogenesis. XIV. Effects of N'-nitrosonornicotine and N'-nitrosonanabasine in rats.

N'-Nitrosonornicotine (NNN) and N'-nitrosoanabasine (NAB) were synthesized and administered in drinking water to male Fischer rats for 30 weeks (total dose, 630 mg). 1,4-Dinitrosopiperazine (DNPI) served as the positive control. By 11 months, all surviving rats given NNN developed esophageal tumors (12/20); 1 had a pharyngeal tumor and 3 had invasive carcinomas originating in the nasal cavity. During the same time, only 1 of 20 rats given NAB developed esophageal tumors. Compared to the strong esophageal carcinogen DNPI, NNN was a moderately active and NAB a weak carcinogen. NNN (0.3-90 parts per million) in chewing tobacco was related to the observation that cancer of the oral cavity and esophagus in man was correlated with the chewing of tobacco.

Anabasine↗

A study of tobacco carcinogenesis. XIII. Tumor-promoting subfractions of the weakly acidic fraction.

The weakly acidic fraction (WAF) of cigarette smoke particulate matter was fractioned by silica get chromatography. We assayed the various primary subfractions for potential tumor-promoting activity by measuring the incorporation of tritiated thymidine into mouse epidermal DNA as induced by these subfractions. Based on these results and on chemical composition, the primary subfractions, were then combined into four major subfractions and tested on initiated mouse skin for tumor-promoting activity by long-term application. Two of these subfractions (40% of WAF) were inactive, whereas the other two (18 and 35% of WAF) showed tumor-promoting activity. The two active portions were then further chromatographed and tested by the short-term bioassay. Some major components of the resulting active fractions included alkyl-2-cyclopenten-2-ol-1-ones, catechols, hydroquinone, fatty acids, and 3-hydroxypyridines. Among these components, catechol, hydroquinone, 3-hydroxypyridine, 6-methyl-3-hydroxypyridine, linolenic acid, and linoleic acid were inactive as tumor promoters in the experimental animal. The activity of the alkyl-2-cyclopenten-2-ol-1-ones is unknown. Other components remain to be identified.

Animals↗

Kinetics of bile acid metabolism in experimental blind loop syndrome.

In an experimental model of the contaminated small bowel syndrome, Eriksson's washout technique was used to study bile salt metabolism. Bile salt secretion rate was increased from 204-7 +/- SD 36-5 mumol/100 g body weight/24 h to 329-9 +/- 146-6, pool size from 33-4 +/- 5-4 mumol/100 g BW to 42-5 +/- 7-2, and biliary flow from 6-6 +/- 1-72 ml/100 g BW/24 h to 8-4 +/- 2.1. Detailed analysis of the washout curves gave indirect evidence of a short-circuit jejunohepatic shunt in the model contaminated small bowel syndrome. Parameters of this shunt were calculated with 9-1 mumol/100 g BW for 'short-circuit' pool size and 13-8 for its circulation frequency.

Animals↗

[Thefts without motive of gain as a psychopathologic syndrome (author's transl)].

Thefts without motive of pain have been known since the early 19th century. But the problem has not been solved. While they were formerly considered a mental disease, today they are not seen as something special. But they still happen. Only a small percentage of common shop-lifting can be called a psycholopathologic syndrome. Many explanations and analyses have been published which are discussed in detail. In a group described here comprehensively difficult marital situations full of conflict, marital sexual frustration, depression, physical and mental exhaustion and aggressive and suicidal tendencies are found. Theft appears to be closely connected with these. But the pattern of motivation and causation is by no means stereo-typed. In order to clear up such actions one will have to consider as exactly as possible the biographic connection and what happens during the act - quite apart from somatic conditions. Present assessment in reports is totally unsatisfactory. To clear up the controversial questions is urgently necessary.

Adolescent↗

N'-nitrosonornicotine in tobacco.

N'-Nitrosonornicotine, a potential carcinogen, has been positively identified in unburned tobacco. The amount in commercial U.S. tobacco products is between 1.9 to 88.6 parts per million, one of the highest values of an environmental nitrosamine yet reported. The amount in food and drink rarely exceeds 0.1 part per million. This compound is the first example of a potential organic carcinogen isolated from tobacco.

Carcinogens↗

Carcinogenicity of methylchrysenes.

Methylchrysenes are present in tobacco smoke and are suspected to contribute to the tumorigenicity of this inhalant. Chrysene and the six isomeric methylchrysenes were obtained in high purity (99.9 percent); they were tested on mouse skin for tumor initiating activity and carcinogenicity. The 3- and 6-methylchrysenes are strong tumor initiators, whereas the other five chrysenes have moderate initiatinig activity. 5-Methylchrysene is a strong carcinogen; the other chrysenes are inactive or weak carcinogens.

Animals↗