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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 379 records · Page 21Linked to original sources
PubMed1978

Evidence for metabolic alpha hydroxylation of N-nitrosopyrrolidine.

Metabolic alpha hydroxylation of cyclic nitrosamines is important in the activation of these compounds to their ultimate carcinogenic forms. Direct evidence for this process is presented. Both alpha-hydroxynitrosopyrrolidine and 3-formyl-1-propanediazohydroxide, which are unstable intermediates resulting from alpha hydroxylation of nitrosopyrrolidine, were generated inaqueous solution from the stable precursors alpha-acetoxynitrosopyrrolidine and 4-(N-carbethoxy-N-nitrosamino)butanal. The major product resulting from the decomposition of slpha-hydroxynitrosopyrrolidine and 3-formyl-1-propanediazohydroxide was 2-hydroxytetrahydrofuran, the cyclic hemiacetal of 4-hydroxy-butyraldehyde. The same product was isolated as its dinitrophenylhydrazone derivative after incubation of rat liver microsomes with nitrosopyrrolidine and after treatment of rats with nitrosopyrrolidine.

Animals↗
PubMed1978

Chemical studies on tobacco smoke LIX. Analysis of volatile nitrosamines in tobacco smoke and polluted indoor environments.

Chemical-analytical data were presented illustrating that the mainstream smoke of tobacco products contains traces of volatile N-nitrosamines. The quantity of volatile nitrosamines in the sidestream smoke of cigarettes and cigars exceeds that in the mainstream smoke by at least a factor of 10. This observation led to model studies and analysis of air in bar cars of trains, in a local bar and other indoor atmospheres polluted by tobacco smoke. The results showed that, during one hour in a smoke-polluted indoor environment, one may inhale volatile nitrosamines in quantities equal to those in the mainstream smoke of 0.5-30 cigarettes. It is emphasized that there are, at present, no epidemiological data linking human respiratory cancers to volatile nitrosamines.

Air Pollution↗
PubMed1978

Chemical studies on tobacco smoke LVI. Tobacco specific nitrosamines: origins, carcinogenicity and metabolism.

Tobacco contains specific carcinogenic nitrosamines which are derived from nicotine. These compounds may be among the causative agents for the various cancers (lung, oral cavity, oesophagus, bladder and pancreas) which are associated with tobacco usage. The major tobacco specific nitrosamine is N'-nitrosonornicotine (NNN), which has been detected in both unburned tobacco (0.3-90.6 ppm) and cigarette mainstream smoke (137-238 ng/cig.). Studies with labelled precursors showed that the major source of NNN formed during curing of tobacco was nicotine, rather than nornicotine. The transfer rate of NNN from tobacco to mainstream smoke was 11.3%; about half the NNN present in smoke therefore originated from tobacco, with the remainder being formed during smoking. Model studies of the reaction of nicotine and nitrite showed that, in addition to NNN, two other nitrosamines, 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)-1-butanal (NNA) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were formed. Analysis of tobacco revealed the presence of NNK in chewing tobacco and snuff (0.6-2.4 ppm). A comparative bioassay of NNN, NNK and NNA in strain A mice indicated that NNK was more tumorigenic than NNN and that NNA was inactive. NNN, which had previously been shown to induce oesophageal and nasal cavity tumours in rats, also was a moderately active carcinogen in the Syrian golden hamster, giving tracheal tumours. A study of the metabolism of cyclic nitrosamines was initiated. Metabolic alpha-hydroxylation of nitrosopyrrolidine, which is thought to be the critical step in activation of this compound, was demonstrated by detection in vitro and in vivo of 2-hydroxytetrahydrofuran, which was the product of decomposition of alpha-hydroxynitrosopyrrolidine. The metabolism of the related cyclic nitrosamine, NNN, is currently under investigation, with emphasis on metabolites resulting from alpha- and beta-hydroxylation. These analytical and metabolic studies are intended to clarify the possible relationship of tobacco-specific nitrosamines and site-specific cancers in tobacco users.

Anabasine↗
PubMed1978

High pressure liquid chromatographic assay for alpha hydroxylation of N-nitrosopyrrolidine by isolated rat liver microsomes.

A high-pressure liquid chromatographic assay for alpha hydroxylation of N-nitrosopyrrolidine by isolated hepatic microsomes was developed. Mixtures consisting of N-nitrosopyrrolidine, microsomes, and an NADPH-generating system were incubated at 37 degrees. The major product of alpha hydroxylation of N-nitrosopyrrolidine, 2-hydroxytetrahydrofuran, was trapped by the addition of 2,4-dinitrophenylhydrazine reagent to form 4-hydroxybutyraldehyde-2,4-dinitrophenylhydrazone. The latter was quantified by reverse-phase high-pressure liquid chromatography. Under optimal conditions, as determined by varying protein and substrate concentrations, the alpha hydroxylation of N-nitrosopyrrolidine was linear for at least 90 min and showed characteristics typical of the microsomal mixed-function oxidase system, such as inhibition by CO and induction by pretreatment of male F-344 rats with Aroclor. N-Nitrosopyrrolidine exhibited type II spectral changes upon interaction with isolated hepatic microsomes. A close correspondence between binding affinity and alpha hydroxylation of N-nitrosopyrrolidine was observed.

Animals↗
PubMed1978

A method for collecting lachrymal fluid from cattle.

The bovine lachrymal duct was catheterised with an expanded polyvinyl catheter and lachrymal fluid was collected for periods of up to 8 h, 45 min. The method was simple and allowed the flow rate of lachrymal fluid to be measured.

Animals↗
PubMed1977

Immunotherapy of bovine ocular squamous cell carcinomas.

Squamous cell carcinomas were collected from the eyes of cattle and saline phenol extracts of the tumours were prepared. The aqueous phase of the extract was used in studies on the immunotherapy of ocular squamous cell carcinomas in cattle. After a single intramuscular injection of the extract, regression and sometimes complete disappearance of eye tumours were observed in 39 of 46 carcinomas. Tumours as large as 4 X 5 cm regressed completely. Enhanced growth of tumours was noted in two of three cattle given multiple injections. Regressing tumours were examined histologically and regression appeared to be associated with a cell-mediated immune reaction. Spontaneous regression of a confirmed squamous cell carcinoma was observed in one animal. This spontaneous tumour in one of the larger domestic animals provides a useful experimental model for the study of tumour antigens.

Animals↗
PubMed1977

Tumorigenic agents in unburned processed tobacco: N-nitrosodiethanolamine and 1,1-dimethylhydrazine.

Two tumorigenic agents, N-nitrosodiethanolamine and 1,1-dimethylhydrazine, have been isolated from tobacco for the first time. The former, a reportedly weak hepatic carcinogen in rats, varied in amounts from a low of 0.1 ppb in flue-cured tobacco not treated with the herbicide MH-30, to a high of 173 ppb in Burley tobacco to which the herbicide had been applied prior to harvesting. MH-30 (maleic hydrazide) used by farmers to remove 'suckers' from tobacco plants, is commonly formulated as the diethanolamine salt. 1,1-Dimethylhydrazine, reported to induce tumors in mice, ranged in amounts from 60 to 147 ppb, except in the case of Burley tobacco where none was detected (detection limit: 0.1 ng). The source of the nitrosamine in the tobacco appears to be the MH-30, whereas that of dimethylhydrazine has not been determined.

Diethylnitrosamine↗
PubMed1977

A study of tobacco carcinogenesis. XV. Effects of N'-nitrosonornicotine and N'-nitrosoanabasine in Syrian golden hamsters.

N'-Nitrosonornicotine (NNN) and N'-nitrosoanabasine (NAB) were synthesized and injected subcutaneously three times weekly in male and female Syrian golden hamsters for 25 weeks (total dose 375 mg). N-Nitrosopiperidine (NPD) served as positive control (total dose 150 mg). Within 83 weeks 12 out of 19 hamsters given NNN had developed tracheal tumors, 1 had a carcinoma of the nasal cavity. During the same time none of the hamsters given NAB developed tumors, whereas all 20 hamsters given NPD developed tracheal tumors and about 50% had additional neoplasms in the nasal cavity. Under the described conditions and in comparison to NPD, NNN appears to be a moderately active tumorigenic agent in the upper respiratory tract of Syrian hamsters, whereas NAB is inactive.

Anabasine↗
PubMed1977

Origin in tobacco smoke of N'-nitrosonornicotine, a tobacco-specific carcinogen.

To evaluate risk factors and to approach methods of reduction of the carcinogenic potential of cigarette smoke, the transfer rate of N-nitrosonornicotine in a popular U.S. blended cigarette into mainstream smoke was quantitatively determined. The mean transfer rate was 11.3%; thus approximately 46% of the tobacco-specific carcinogen in the smoke came from the tobacco, and the remainder was synthesized during smoking.

Nicotine↗
PubMed1977

Induction of tumors in mice with the herbicide succinic acid 2,2-dimethylhydrazide.

A solution of 2% succinic acid 2,2-dimethylhydrazide was given continuously in the drinking water of 6-week-old randomly bred albino mice for the remainder of their lives. The treatment gave rise to tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in the controls were 6, 18, and 0%, whereas in the treated groups the corresponding tumor incidences were 73, 73, and 5%. Light microscopic examination revealed typical angiomas and angiosarcomas of blood vessels, adenomas and adenocarcinomas of lungs, and adenomas of kidneys. The study thus demonstrates the tumorigenicity of the herbicide, succinic acid 2,2-dimethylhydrazide. Since the residues of this chemical occur in fruit, the human population is exposed to it. The environmental implication of this finding and the fact that the hydrazines as a class have tumorigenic properties are discussed.

Adenocarcinoma↗
PubMed1976

[Role of phagocytosis and soluble antibacterial factors in experimental immunization of Locusta migratoria].

Last instar larvae of Locusta migratoria can be protected ("vaccinated") against lethal doses of Bacillus thuringiensis by previous injections of low doses of this pathogen. If iron saccharate is injected in to larvae prior to the administration of the "vaccinating" dose of Bacillus thuringiensis, no antibacterial protection can be induced. Injection of iron saccharate in to "vaccinated" larvae does not interfere with the induced protection; such larvae resist lethal doses.

Animals↗