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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 307 records · Page 17Linked to original sources
PubMed1983

Endogenous formation of N-nitrosoproline in cigarette smokers.

It was the goal of this study to assay the potential of inhaled cigarette smoke for endogenous N-nitrosation of amines in smokers by means of measuring urinary excretion of N-nitrosoproline (NPRO). For 12 days, nonsmoking and smoking men were placed on a controlled diet which was relatively low in proline and in ascorbic acid. On Days 1 through 3, the volunteers received the controlled diet alone (Group 1); on Days 4 through 6, the diet was supplemented by a single daily dose of 300 mg of proline (Group 2); on Days 7 through 9, the diet was supplemented by a single daily dose of 1 g of ascorbic acid followed by 300 mg of proline (Group 3); and for the last 3 days, a single daily dose of 1 g ascorbic acid was given (Group 4). Collections of 24-hr urine were made on Days 3, 6, 9, and 12 of the study. The urine was analyzed for NPRO and creatinine and for cotinine, the major metabolite of nicotine. The mean 24-hr NPRO excretion for 13 nonsmokers in Group 1 was 3.6 micrograms. The NPRO excretion in 13 smokers in Group 1 was found to be 5.9 micrograms/24 hr, which is significantly higher than that of the nonsmokers (p less than 0.05). Urinary NPRO in 14 nonsmokers of Group 2 was significantly lower than that of the 14 smoking volunteers (p less than 0.05). Data for Group 3 indicated that those smokers who had shown elevated NPRO excretion in Group 2 had reduced urinary levels of NPRO as a consequence of ascorbic acid intake. Differences in NPRO excretion by smokers and nonsmokers on controlled diet with ascorbic acid but without proline supplements (Group 4) were also insignificant. These findings suggest that the documented endogenous N-nitrosation of proline which occurs as a result of cigarette smoke inhalation may also apply to other N-nitrosatable amines including nicotine and thus lead to in vivo formation of carcinogenic N-nitrosamines.

Ascorbic Acid↗
PubMed1982

Efflux of choline from neurons and glia in culture.

The efflux of radioactive choline from exclusively neuronal or glial cell cultures was dependent upon the concentrations of choline present in the cells and in the incubation medium, suggesting the possible presence of a homoexchange phenomenon between influx and efflux. The ionic dependence of the outward movement of choline from these cells showed that is could be stimulated by high K+ concentrations and by the absence of Ca2+. In glial cells, however, the efflux of choline was increased with a much lower concentration of K+ compared to neurons. The result may suggest that during nerve stimulation the release of K+ from neurons could stimulate, from glia, the efflux of choline which would then be taken up in neurons.

Animals↗
PubMed1982

Mutagenicity of substituted carbazoles in Salmonella typhimurium.

Mutagenic activities of 1-, 2-, 3-, 4-, and 9-methylcarbazole were evaluated in S. typhimurium TA1535, TA1537, TA1538, TA98, and TA100. Only 9-methylcarbazole was found to be mutagenic in S. typhimurium TA100 in the presence of rat-liver homogenate. Mutagenic activity was also observed in TA100 for 2,9-, 3,9-, and 4,9-dimethylcarbazole. None of these methylated carbazole derivatives was mutagenic in TA1535, TA1537, TA1538 and TA98 in either the presence of absence of rat-liver homogenate. These results indicate that a 9-methyl substituent is associated with the mutagenic activity of these carbazole derivatives. Comparative studies on the mutagenic activity of 9-substituted carbazoles demonstrated that the activity of 9-ethylcarbazole was less than that of 9-methylcarbazole. 9-Phenyl- and 9-i-propylcarbazole were inactive under identical assay conditions. 9-Hydroxymethylcarbazole, a major metabolite of 9-methylcarbazole, was confirmed to be a direct-acting mutagen in S. typhimurium TA100. 9-Formylcarbazole was inactive as a mutagen when assayed with or without metabolic activation. These data are consistent with the finding that 9-hydroxymethylcarbazole is a major proximate mutagenic form of 9-methylcarbazole.

Animals↗
PubMed1982

Comparative tumor initiating activity on mouse skin of 6-nitrobenzo[a]pyrene, 6-nitrochrysene, 3-nitroperylene, 1-nitropyrene and their parent hydrocarbons.

6-Nitrobenzo[a]pyrene, 6-nitrochrysene, 3-nitroperylene, 1-nitropyrene, and the corresponding parent hydrocarbons were tested for tumor initiating activity on mouse skin with promotion by tetradecanoylphorbol acetate. The initiating doses of 6-nitrobenzo[a]pyrene and benzo[a]pyrene were 0.05 mg each; for all other compounds the initiating doses were 1.0 mg. 6-Nitrochrysene induced tumors in 60% of the mice (2.1 tumors per mouse), but was significantly less tumorigenic than chrysene. 3-Nitroperylene induced tumors in 42% of the mice (0.5 tumors per mouse) and was significantly more active than perylene. Neither 1-nitropyrene nor 6-nitrobenzo[a]pyrene exhibited significant tumorigenic activity in the concentrations tested.

Animals↗
PubMed1982

Cadmium and nickel in smoke of cigarettes prepared from tobacco cultured on municipal sludge-amended soil.

Cigarettes prepared from tobacco grown on municipal sludge-amended soil were smoked, and the mainstream particulates and gaseous fractions were analyzed for total cadmium and nickel content. Sludge-grown and control (soil-grown) tobaccos contained, respectively, 67.4 and 3.18 ppm of cadmium and 19.4 and 1.29 ppm of nickel. The quantities of cadmium (microgram per cigarette) found in the mainstream particulate and gaseous fractions were, respectively, 6.67 and 0.04 for the sludge-grown and 0.21 and 0.03 for the control treatments. The quantities of nickel (microgram per cigarette) found in the mainstream particulates and gaseous fractions were, respectively, 0.11 and 0.07 for the sludge-grown and 0.01 and 0.01 for the control treatments. The potential public health implications of these results and modifying factors are discussed.

Cadmium↗
PubMed1982

Tumour initiating activity of dihydrodiols of benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene.

The tumor initiating activities on mouse skin of benzo[b]fluoranthene, (B[b]F), benzo[j]fluoranthene (B[j]F), benzo[k]fluoranthene (B[k]F] and three of their dihydrodiols, 9,10-dihydro-9,10-dihydroxybenzo[b]fluoranthene (B[b]F-9,10-diol), 9,10-dihydro-9,10-dihydroxybenzo[j]fluoranthene (B[j]F-9,10-diol), and 8,9-dihydro-8,9-dihydroxybenzo[k]fluoranthene (B[k]F-8,9-diol) were evaluated. Among the parent hydrocarbons, B[b]F was the most potent tumor initiator, with activity greater than that of B[j]F but less than that of benzo[a]pyrene. B[k]F also showed tumor initiating activity, in contrast to its lack of complete carcinogenic activity on mouse skin. B[b]F-9,10-diol, which can form a bay region dihydrodiol epoxide, was as active as B[b]F. B[j]F-9,10-diol, which would form its dihydrodiol epoxide in a four sided pseudo-bay region, was less active than B[j]F. B[k]F-8,9-diol was inactive. These results, together with parallel metabolic studies, suggest that the formation of bay region dihydrodiol epoxides may not be the major activation mechanism in benzofluoranthene tumorigenesis.

Animals↗
PubMed1982

N-Nitrosomorpholine and other volatile N-nitrosamines in snuff tobacco.

Ten popular snuff brands from the USA and Sweden were analyzed for volatile N-nitrosamines (VNA). Seven of these samples contained between 20 and 70 p.p.b. of N-nitrosomorpholine (NMOR), a strong animal carcinogen. Some of the snuff containers which were made of waxed cardboard contained morpholine. This observation and a model study with the container waxes plus [14C]morpholine indicate that NMOR possibly can be formed by way of diffusion of the morpholine into the snuff and subsequent N-nitrosation. The VNA including NMOR (60-1150 p.p.b.) together with N-nitrosodiethanolamine (NDELA; 225-3300 p.p.b.) and the four tobacco-specific N-nitrosamines (TSNA; 1300-80,000 p.p.b.) contribute significantly to the carcinogenic potential of snuff. This tobacco product, although a known human carcinogen, is becoming increasingly popular especially among young people in the USA and Sweden. A recently introduced Swedish brand with individual snuff portions wrapped in aluminum foil was free of VNA (less than 2 p.p.b.) and contained relatively low levels of NDELA (290 p.p.b.) and TSNA (4200 p.p.b.). This indicates that practical approaches towards lowering N-nitrosamine levels in these snuff products are available.

Carcinogens↗
PubMed1982

Identification of the mutagenic metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene.

The metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene obtained upon incubation with liver homogenate from Aroclor pretreated rats were assayed for mutagenicity in Salmonella typhimurium TA100. The mutagenic metabolites of fluoranthene and 2-methylfluoranthene were identified as 2,3-dihydro-2,3-dihydroxyfluoranthene and 4,5-dihydro-4,5-dihydroxy-2-methylfluoranthene, respectively. In contrast to these results, the major proximate mutagen detected among the in vitro metabolites of 3-methylfluoranthene was 3-hydroxymethylfluoranthene. Comparison of the mutagenic potential of 2-hydroxymethylfluoranthene demonstrated that the latter was a more powerful mutagen. Quantitative analyses of the metabolites of fluoranthene with that of 3-hydroxymethylfluoranthene demonstrated that the latter was a more powerful mutagen. Quantitative analyses of the metabolites of fluoranthene, 2-methylfluoranthene, and 3-methylfluoranthene indicated that similar amounts of dihydrodiols were formed. 4,5-Dihydro-4,5-dihydoxy-3-methylfluoranthene, however, was not found to be a potent mutagenic metabolite. These data suggest that the activation pathway to ultimate mutagens may differ for 2- and 3-methylfluoranthene.

Animals↗
PubMed1982

N-nitrosamines: environmental occurrence, in vivo formation and metabolism.

A number of amines and quaternary ammonium salts can be nitrosated to N-nitrosamines under environmental conditions as well as in vivo. Of the N-nitrosamines which have been bioassayed to date, more than 250 are proven animal carcinogens. In the absence of data which document that N-nitrosamines can be carcinogenic to man, we concur with the International Agency for Research on Cancer that those nitrosamines that were proven carcinogens in at least 2 animal species "should be regarded for practical purposes as if they were carcinogenic to humans" (1). Such evaluation pertains also to N-nitrosodiethanolamine (NDELA), N-nitrosomorpholine (NMOR) and the tobacco-specific N-nitrosamines (TSNA). This presentation discusses the environmental occurrence, analysis, reduction, bioassay data for carcinogenicity and metabolism of these 3 types of nitrosamines. The data at hand make it prudent to encourage reduction of the occurrence of N-nitrosamines in the workplace, in the environment and in food, tobacco and other personal use products. Emphasis should also be placed on research efforts to inhibit the in vivo formation of N-nitrosamines and their metabolic activation to reactive carcinogenic species. The latter efforts require increased knowledge as to the activation of nitrosamines and their reaction with cellular macromolecules including DNA.

Animals↗
PubMed1982

Tobacco specific N-nitrosamines: occurrence and bioassays.

A new GC-TEA method for the analysis of tobacco-specific N-nitrosamines (TSNA) has been developed. Four TSNA have thus far been identified; these are N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosoanatabine (NAT) and N'-nitrosoanabasine (NAB). The method is currently being applied to the development of cigarette filter-tips which will selectively remove these carcinogens from cigarette smoke. Since recent epidemiological studies have established a correlation between snuff dipping and oral cancer, we have analysed leading snuff brands for TSNA. Snuff products from Sweden, Denmark, Bavaria and the USA contained 5-106 mg/kg of the TSNA and the saliva of snuff dippers had TSNA levels of 20-890 micrograms/kg. NNN, NNK and NAB induce benign and malignant tumours of the respiratory tract of mice and rats. We have shown that NNN and NNK induce tumours in the upper respiratory tract of hamsters and that NNK is the most active carcinogen of the TSNA, also inducing adenoma and adenocarcinoma in the hamster lung. The reported chemical analyses and bioassay results support the epidemiological findings on the causal association of tobacco use and cancer in man.

Adult↗