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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 235 records · Page 13Linked to original sources
PubMed1986

The reemergence of smokeless tobacco.

Smokeless tobacco (snuff and chewing tobacco) is reemerging as a popular form of tobacco, particularly among male adolescents. In different regions of the United States, from 8 to 36 percent of male high-school students are regular users. The use of smokeless tobacco has been shown to cause oral-pharyngeal cancer. The strongest link is with cancers of the cheek and gum. White mucosal lesions (leukoplakia) are found in 18 to 64 percent of users, often at the site where the tobacco was held. Other associations have been suggested for cancers of the esophagus, larynx, and pancreas. Nitrosamines, found in high concentrations in smokeless tobacco, most likely have a role in its carcinogenicity. Other health problems include periodontal disease, acute elevations of blood pressure, and dependence. In early 1986, after action at the state level, Congress enacted a federal law requiring health-warning labels on packages of smokeless tobacco and a ban on electronic advertising. Other regulatory measures under consideration include raising state and federal excise taxes, tightening controls on advertising, and prohibiting sales to minors. In view of the recent growth of this problem, policy makers are taking the opportunity to intervene with preventive measures to protect a new generation of tobacco users.

Adolescent↗
PubMed1986

Toxicity studies on clove cigarette smoke and constituents of clove: determination of the LD50 of eugenol by intratracheal instillation in rats and hamsters.

Eugenol, eugenol acetate, beta-caryophyllene, and alpha-humulene are constituents of clove and clove cigarette smoke. The toxicity of these compounds was evaluated by intratracheal instillation in male F-344 rats. Eugenol was most toxic in this assay. The LD50 of eugenol was 11 mg/kg in male F-344 rats and 17 mg/kg in male Syrian golden hamsters. Congestion of the lung with interstitial hemorrhages, acute emphysema, and acute pulmonary edema were among the macroscopic and histologic findings observed in the animals after intratracheal administration of eugenol. Similar effects were not observed with male Syrian golden hamsters exposed to clove cigarette smoke. The estimated daily intake of eugenol for those hamsters exposed to clove cigarette smoke was below 2 mg/kg.

Animals↗
PubMed1986

Uptake of ethanolamine in neuronal and glial cell cultures.

The uptake of radioactive ethanolamine has been studied in exclusively neuronal and glial cell cultures from dissociated cerebral hemispheres of chick embryos. Both cell types show saturable kinetics; neurons have an apparent Km of 6.7 microM, Vmax 41.4 pmol mg prot.-1 min-1 and glial cells a Km of 119.6 microM, Vmax 3,917 pmol mg prot-1 min-1. The lower affinity of the transport and the 100 fold increase in Vmax observed in glial cells correlated with a more important accumulation of free ethanolamine found in glial cells and with a higher degree of phosphorylation of ethanolamine. The uptake appeared to be temperature and Na+ ions dependent but was not affected by CN- or ouabain. Monomethyl-, dimethylethanolamine and choline were effective in inhibiting the uptake. Little or no effect was observed with serine, methionine, carnitine, alanine or glutamate.

Animals↗
PubMed1986

Effects of the co-carcinogen catechol on benzo[a]pyrene metabolism and DNA adduct formation in mouse skin.

We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene) on the metabolic activation of [3H] benzo[a]pyrene (BaP) in mouse skin, in vivo and on the binding of BaP metabolites to DNA and protein at intervals from 0.5-24 h. Upon topical application of 0.015 mg [3H]BaP and 0.25 or 0.5 mg catechol per mouse, catechol had little effect on the total amount of [3H]BaP metabolized in mouse skin, but it affected the relative proportions of [3H]BaP metabolites. Catechol (0.5 mg/mouse) decreased the proportion of water-soluble [3H]BaP metabolites, ethyl acetate-soluble polar metabolites and quinones, but doubled the levels of unconjugated 3-hydroxy-BaP at all measured intervals after treatment. Catechol also caused a small increase in the levels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP 0.5 h after treatment. Two hours after treatment, the levels of these metabolites subsided to those of the controls. Catechol did not affect the levels of glutathione conjugates of BaP. However, it caused a decrease in glucuronide and sulphate conjugate formation from BaP. Catechol caused an approximately 2-fold increase in the formation of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNA adducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivity associated with epidermal proteins after [3H]BaP application. Because catechol increased levels of 3-hydroxyBaP, we considered the possibility that 3-hydroxyBaP might enhance the tumor initiating activities of BaP or BPDE in mouse skin; a bioassay demonstrated that this was not the case. The results of this study indicate that one important effect of catechol related to its co-carcinogenicity is its ability to enhance formation of anti-BPDE-DNA adducts in mouse skin.

Animals↗
PubMed1986

Contribution of passive smoking to respiratory cancer.

This article reviews data from experimental and epidemiologic studies on passive smoking and makes 12 recommendations for further study. The physicochemical nature of passive smoke, the smoke inhaled by nonsmokers, differs significantly from the mainstream smoke inhaled by the active smoker. At present, measurement of urinary cotinine appears to be the best method of assessing exposures to passive smoking. Data indicate that the greater number of lung cancers in nonsmoking women is probably related to environmental tobacco smoke. Exposures in utero and very early in life to passive smoking may be important in relationship to the subsequent development of cancer and need further consideration. The short-term effects of environmental tobacco smoke on the cardiovascular system, especially among high-risk individuals, may be of greater concern than that of cancer and requires further study. Further study of increased risks of lung cancers in relation to environmental tobacco smoke exposure requires larger collaborative studies to identify lung cancer cases among nonsmokers, better delineation of pathology, and more careful selection of controls. In addition, studies of epithelial cells or specific cytology should be undertaken to determine evidence of cellular changes in relation to environmental tobacco smoke exposure. Animal inhalation studies with passive smoke should be initiated with respect to transplacental carcinogenesis, the relationship of sidestream smoke exposure with lung cancer, the induction of tumors in the respiratory tract and other organs, and the differences in the physicochemical natures of sidestream and mainstream smoke.

Air Pollutants↗
PubMed1986

Carcinogenic agents in snuff.

The oral use of snuff has been associated with an increased-risk for cancer of the oral cavity and pharynx. The five most popular U.S. snuff brands were analyzed for alkaloids, volatile and tobacco-specific N-nitrosamines (TSNA), benzo[a]pyrene (CAS: 50-32-8), and polonium-210. The carcinogenic TSNA in the five snuff brands ranged from 9,600 to 289,000 ppb. These concentrations exceed the nitrosamine concentrations of other consumer products by at least 2 orders of magnitude. Polonium amounted to 0.16-1.22 pCi/g dry snuff. Trace amounts of benzo[a]pyrene (0.1-63 ppb) were indicative of contamination of the tobacco with thermal degradation products, probably due to fire curing or flue curing. The findings from this study, the biologic activity of snuff in animal models, and the epidemiologic studies on snuff use and oral cancer strongly suggest the need for reduction of carcinogens and especially of nitrosamines and polonium-210 in snuff.

Benzo(a)pyrene↗
PubMed1986

Chemical constituents and bioactivity of tobacco smoke.

Tobacco smoke contains more than 3900 constituents. In this presentation we have summarized our present knowledge as to the physicochemical nature of tobacco smoke and specific agents therein. Emphasis has been placed on the discussion of formation and identification of toxic and, especially, of tumorigenic agents in tobacco smoke. In the concluding Table 13 we have listed those smoke constituents in the mainstream smoke of cigarettes that we regard as important contributors to the toxic and carcinogenic potential of tobacco smoke. This judgement is based on extensive laboratory studies. Finally, data are presented in support of the concept that product modification can reduce the carcinogenic potential of cigarettes. However, it must be emphasized that the only safe way to avoid the cancer risks associated with smoking is to refrain from smoking.

Carcinogens↗
PubMed1986

Induction of oral cavity tumors in F344 rats by tobacco-specific nitrosamines and snuff.

The tumorigenic activities toward the oral cavity of snuff, its extracts, and two of its major nitrosamines, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were evaluated in male F344 rats. In one protocol, groups of 21-30 rats were treated beginning at age 10 weeks by chronic application to the oral cavity for 131 weeks of either H2O, an H2O extract of snuff, an H2O extract of snuff enriched with ten times its indigenous concentration of NNN and NNK, or with NNN and NNK in H2O. The incidence of oral cavity tumors in the rats treated with NNN and NNK was 8 of 30, compared to 0 of 30 in controls (P less than 0.05). These results demonstrate that NNN and NNK can induce tumors locally in the oral cavity of F344 rats. Oral cavity tumors were also observed in 3 of 30 rats treated with snuff extract enriched with NNN and NNK, but not in the rats treated with snuff extract alone. In a second protocol, a test canal was surgically created in the lower lip of groups of 21-32 rats, and either snuff, H2O-extracted snuff, or snuff enriched with its own H2O extract was inserted in the test canal 5 times weekly for 116 weeks. A group of 10 control rats had surgery only. Among the 32 rats treated with snuff, 3 had oral cavity tumors; one was a squamous cell carcinoma originating in the test canal and invading the gingiva, one was a papilloma of the test canal, and one was a papilloma of the hard palate. Oral cavity tumors were also observed in 2 of 21 rats treated with H2O-extracted snuff and 1 of 32 rats treated with snuff enriched with its H2O extract. Oral tumors were not observed in control rats. The results of this study indicate that snuff and individual nitrosamines present in snuff can induce oral cavity tumors in F344 rats and support the epidemiological observations which indicate that snuff dipping causes oral cancer in man.

Animals↗
PubMed1986

Identification and quantitative determination of aniline and toluidines in human urine.

Aniline and o-, m-, and p-toluidine, which are representative of aromatic amines in cigarette smoke, were identified and quantified in human urine. Smokers excreted 3.1 +/- 2.6 micrograms/24 h of aniline and 6.3 +/- 3.7 micrograms/24 h of o-toluidine (n = 16). Nonsmokers excreted 2.8 +/- 2.5 micrograms/24 h of aniline and 4.1 +/- 3.2 micrograms/24 h of o-toluidine (n = 12). Meta- and p-toluidine were detected in the urine of 2 of 11 smokers and 4 of 9 nonsmokers. The observed intra- and interindividual variations in the amounts of urinary aniline and o-toluidine were relatively large. The results of this study demonstrate for the first time that aniline and toluidines are present in human urine and suggest that sources other than cigarette smoke contribute significantly to their concentrations in urine.

Adult↗
PubMed1986

The effect of nass use and smoking on the risk of oral leukoplakia.

The results of a survey of a population with a high incidence of oral cancer are presented in this paper. A remarkably high proportion (41%) of the men surveyed used nass, which is a mixture of tobacco, lime, ash, and cotton oil. The prevalence of oral leukoplakia, lesions thought to be a precursor of oral cancer, was high in persons who used nass (12%) and who smoked cigarettes (15%), and highest among those men who both used nass and smoked (21%). It has been shown that nass use increases the frequency of micronucleated cells in the exfoliated sublingual cells. The clastogenic and genotoxic effect of nass revealed in the study could be attributed to the presence of tobacco-specific N-nitroso compounds. However, the results of chemical analysis, which has shown that nass contains relatively low levels of these compounds, suggest that the relatively strong genotoxic activity of nass could primarily be associated with other chemicals, possibly oxidized phenolics. Despite the uncertainty as to which of the chemicals contained in nass are involved in the etiology of oral cancer and what exactly are the mechanisms of nass-induced carcinogenesis, the results of this study suggest that in populations where nass is widely used, oral leukoplakia and, most probably, oral cancer are conditions that could be prevented by the elimination of nass use and cigarette smoking.

Aged↗
PubMed1985

Solubilized ketanserin binding sites from pig platelet membranes.

Plasma membranes of pig platelets were isolated and subjected to solubilization with digitonin. Binding of [3H]ketanserin to the solubilized membrane fraction, optimal at pH 7.5, was time and protein dependent and was greatly reduced by increasing ionic strength of the incubation buffer. Saturation analysis and inhibition of binding with various 5-HT2 antagonists showed the presence of two binding sites with high and low affinity, respectively. High affinity binding to solubilized membrane proteins correlated well with that found in native membranes with regard to the dissociation constant KD (1.6 and 1.2 nM, respectively) and the displacement by 5-HT2 antagonists. Binding to this site was not inhibited by the dopamine antagonist haloperidol which, however, displaced [3H]ketanserin bound to the low affinity site. At present the nature of the low affinity binding site (KD = 71 nM) is not well understood. Centrifugation on sucrose gradients revealed only one peak of [3H]ketanserin binding corresponding to the molecular weight of catalase (232,000 Da), thus probably reflecting a close association of the two binding sites.

Animals↗
PubMed1985

Pharmacokinetics of N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in laboratory animals.

The pharmacokinetics of N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the Syrian golden hamster, the CD-1 mouse, and the baboon were compared to the pharmacokinetics in the Fischer rat. The formation and biological half-life of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the major metabolite of NNK, was also studied in these animal species. The biological half-life of NNN in these 4 animal species ranged from 0.24 h to 3.06 h, that of NNK from 0.21 h to 0.43 h and NNAL from 0.48 h to 2.9 h. The pharmacokinetic data obtained in the baboon suggest that treatment with NNN and NNK causes an enzyme induction which accelerates the rate of elimination of these compounds.

Animals↗