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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 163 records · Page 9Linked to original sources
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

A study of betel quid carcinogenesis. IX. Comparative carcinogenicity of 3-(methylnitrosamino)propionitrile and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone upon local application to mouse skin and rat oral mucosa.

The Areca-derived 3-(methylnitrosamino)propionitrile (MNPN) was tested for its tumor initiating activity on mouse skin and for its tumorigenic potential in the oral mucosa of rats. On mouse skin, like the otherwise strongly carcinogenic, tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), MNPN showed only weak local tumor initiator activity. However, the application of MNPN to mouse skin led also to multiple distant tumors in the lungs of the animals. Twice daily swabbing of the oral cavity of rats with aqueous solutions of MNPN or NNK for up to 61 weeks led only to one oral tumor in each group of 30 animals. Yet, these N-nitrosamines proved again to be strong organ-specific carcinogens. Thus, MNPN induced nasal tumors in 80% of the rats and lung adenomas in 13%, liver tumors in 10% and papillomas of the esophagus in 7%. NNK induced lung adenoma and/or adenocarcinoma in 90%, nasal tumors in 43% and liver adenomas/adenocarcinomas in 30% of the rats. These results confirm previous observations that, independent of the site and mode of application, MNPN and NNK remain strong organ-specific carcinogens in laboratory animals.

Administration, Topical↗
PubMed1991

Detection of direct mutagenicity of cigarette smoke condensate in mammalian cells.

Mutagenicity of cigarette smoke condensate (CSC) and the acidic, basic and neutral fractions of CSC was examined in the AL hybrid cell, a Chinese hamster ovary cell containing one human chromosome 11. Since the human chromosome 11 is not necessary for survival of the AL cells, mutations involving large deletions and chromosomal loss by non-dysjunction are non-lethal events that are detectable by loss of human cell surface antigens (a1, a2 and a3) encoded by genes on chromosome 11p (a1 and a3) and 11q (a2) through an antibody-complement lysis assay. Exposure of AL cells to CSC without exogenous metabolic activation caused a dose-dependent cytotoxicity and mutagenicity. Mutagenicity also increased with time of incubation up to 3 h with a maximum of 300 a1- mutants/10(5) survivors (250% above background; P less than 0.0005) after incubation with 100 micrograms/ml CSC. Cytotoxicity and mutagenicity of CSC were inversely proportional to cell density. Fifty percent lethal doses for the acidic, basic and neutral fractions of CSC after 3 h of incubation were 30, 100 and 240 micrograms/ml respectively, and the acidic fraction at a concentration of 25 micrograms/ml induced 350 a1- mutants/10(5) survivors (230% above background; P less than 0.0005); the basic and neutral fractions were less mutagenic. These results indicate that CSC and fractions of CSC can directly produce a spectrum of mutations, through both deletional and non-dysjunctional mechanisms of a kind known to lead to inactivation of tumor suppressor genes.

Animals↗
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

Nicotine-derived N-nitrosamines (TSNA) and their relevance in tobacco carcinogenesis.

Biochemical studies and bioassays support the concept that the increased risk for cancer of the oral cavity in snuff dippers and cancer of the lung, upper aerodigestive tract, and pancreas in smokers is most likely associated with the exposure to tobacco-specific N-nitrosamines. The doses of TSNA required to induce tumors in the oral cavity in rats and tumors in the lungs of rats and hamsters are comparable to the total doses of TSNA to which a long-term snuff dipper, respectively a cigarette smoker, are exposed over 4 decades. The carcinogenic NNN and NNK are metabolized to highly reactive electrophiles which react with nucleophilic centers of DNA and with proteins. The DNA-adducts are known to cause miscoding which can activate K-ras proto-oncogenes. K-ras oncogenes have been detected in adenocarcinomas of the lung of smokers. TSNA also form globin adducts in the blood of laboratory animals as well as of snuff dippers and smokers. Such adducts are currently being evaluated for their significance as biochemical markers of exposure to TSNA. These biomarkers may also serve as indicators for the possible endogenous formation of TSNA in tobacco chewers and smokers. Additional research needs in TSNA carcinogenesis include the development of modified methods for the reduction of TSNA in tobacco and smoke, inhibition of TSNA carcinogenesis by nutrients and micro-nutrients and the testing of chemopreventive agents.

Animals↗
PubMed1991

Lung cancer and the changing cigarette.

Epidemiological studies have shown that the long-term smoker of low-yield cigarettes has a 20-50% lower risk of lung cancer than the smoker of high-yield cigarettes. This risk reduction is attributed to changes in the make-up of cigarettes and especially to the introduction of filter tips. Other changes relate to the use of tobaccos that produce lower smoke yields, including reconstituted and expanded tobaccos, as well as utilization of porous cigarette paper and perforated filter tips. New developments in the make-up of commercial cigarettes must be monitored in order to prevent unfavourable introductions. Although a smoke-free society should be the major public health goal, recent consumer statistics do not support this goal. Thus, a strong social case is made for further developments in the low-yield cigarette.

Humans↗
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↗
PubMed1991

N-nitroso compounds and tobacco-induced cancers in man.

Human exposure to N-nitroso compounds in tobacco products is more intense and widespread than from any other known source. This paper presents evidence that two of these N-nitroso compounds, 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine are involved in causing cancers of the oral cavity, lung, oesophagus and pancreas in tobacco users. The reduction or elimination of these nitrosamines from tobacco products would probably lead to a decrease in the incidence of these cancers.

Carcinogens↗
PubMed1991

Extensive spontaneous occlusive arteriosclerosis of the lingual arteries in Fischer rats, a model for the study of human occlusive arteriosclerosis of medium- and small-sized arteries.

Spontaneous occlusive arteriosclerosis is rarely present in rats or other laboratory rodents. Instead, the common vascular lesion in these animals is a mineralization resembling Mönkeberg's medial calcinosis, or non-atheromatous and non-obstructive arteriosclerosis. For reasons yet unknown, the lingual arteries of Fischer rats behave differently; they develop extensive sclerotic lesions with progressive narrowing of the lumen, leading to complete occlusion and sometimes recanalization, comparable to lesions seen in human coronaries, carotids, tibials, etc. The spontaneous plaque-forming, thrombotic, occlusive arteriosclerosis of the lingual artery in Fischer rats can serve as an experimental model for the same lesion of medium- and small-sized arteries in man. As such, it can considerably facilitate the testing of nutritional, hormonal, immunological and other chemical or physical factors for a possible role in promoting or inhibiting the thrombotic-occlusive arteriopathy in man.

Animals↗
PubMed1990

Insect immunity. Characterization of a Drosophila cDNA encoding a novel member of the diptericin family of immune peptides.

Drosophila shows an immune response when challenged by injection of low doses of bacteria. To date, the molecules involved in this immune reaction have remained elusive, with the exception of cecropins (4-kDa antibacterial peptides initially isolated from the moth Hyalophora cecropia) for which three closely related genes have been characterized recently. We report the molecular cloning and sequencing of a cDNA from a library of immune Drosophila which encodes a novel member of the family of diptericins (9-kDa antibacterial peptides initially isolated from the fly Phormia terranovae). Transcripts for the Drosophila diptericin are detected 2 h after injection of bacteria. They are apparently derived from a single gene mapping at position 56 A on the right arm of the second chromosome. We discuss the existence of a distant relationship between the diptericins and two other groups of anti-bacterial insect proteins, the attacins, and the sarcotoxins II.

Amino Acid Sequence↗
PubMed1990

Dose-response study of DNA and hemoglobin adduct formation by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in F344 rats.

Levels of hemoglobin adducts and DNA adducts were measured in F344 rats after 4 consecutive daily i.p. injections of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The dose range was from 3 to 10,000 micrograms/kg/day. [5(-3)H]NNK and [C3H3]NNK were used to measure pyridyloxobutylation and methylation, in both globin and DNA, respectively. In globin, the level of binding increased linearly with dose. Total binding of [5(-3)H] NNK to globin was 3.2 to 8900 fmol/mg and total binding of [C3H3]NNK was 3.5 to 20,000 fmol/mg. The extents of pyridyloxobutylation of both DNA and globin were determined by measuring the amounts of 4-hydroxy-1-(3-pyridyl)-1-butanone released from each, over the dose range 15-5000 micrograms/kg/day. The levels of 4-hydroxy-1-(3-pyridyl)-1-butanone released were 3.2-650 fmol/mg globin, 18-3400 fmol/mg liver DNA, and 58-2180 fmol/mg lung DNA. The extents of DNA methylation in both lung and liver were greater than pyridyloxobutylation. When the dose range was 3-5000 micrograms/kg/day, the levels of 7-methylguanine were 0.22-246 pmol/mumol guanine (149-167,000 fmol/mg) in liver DNA and 0.23-78 pmol/mumol guanine (160-53,000 fmol/mg) in lung DNA. In the lung, the ratio of methylation to pyridyloxobutylation decreased as the dose decreased. In contrast to globin adduct formation, DNA adduct formation did not increase linearly with dose; adduct formation was greater at lower doses than would have been predicted by extrapolation from higher doses. Thus the results of this study demonstrate that there was not a linear relationship between globin adduct formation, neither pyridyloxobutylation nor methylation, and DNA adduct formation in the liver or the lung of rats treated with NNK.

Animals↗
PubMed1990

Oxidation and DNA binding of (+)-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene in mouse epidermis in vivo and effects of coadministration of catechol.

Using a stereochemical probe as described by Marnett (Carcinogenesis (Lond.), 8: 1365-1373, 1987), we have investigated the mechanism of oxidation of (+)-[3H]BaP-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene [(+)-[3H]BaP-7,8-diol] in mouse epidermis in vivo. Groups of mice were topically treated with (+)-[3H]BaP-7,8-diol (60 nmol/mouse) and sacrificed at intervals from 1/2 to 8 h post treatment. (-)-Anti- and (+)-syn-7,8-[3H]dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) were formed as metabolites in a ratio of about 4 to 1, respectively, as determined by HPLC analysis of the hydrolysis products. Pretreatment of mice with indomethacin, an inhibitor of prostaglandin H synthase, did not alter the ratio of anti- to syn-BPDE-derived hydrolysis products. Pretreatment of mice with the cytochrome P-450 inducer, beta-naphthoflavone, yielded twice the level of syn-[3H]BPDE in mouse skin at the 1/2-h survival point. However, this enhancing effect diminished over time. Coadministration of 1,2-dihydroxybenzene (catechol) with (+)-[3H]BaP-7,8-diol decreased the formation of (-)-anti-[3H]BPDE and also decreased lipid peroxidation, as measured by the extent of formation of thiobarbituric acid-reactive material in mouse epidermis. Analysis of mouse epidermal DNA adducts 24 h after topical application (+)-[3H]BaP-7,8-diol indicated that the major adduct is not formed from the major metabolite (-)-anti-BPDE. Acid hydrolysis of the major adduct resulted in the formation of a small amount of r-7,c-9,c-10,t-8-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene and two unidentified products different from 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro-BaP. Coadministered catechol suppressed the formation of this adduct by 30%. The present observation suggests that a peroxyl radical-mediated epoxidation pathway is involved in the oxidation of (+)-[3H]BaP-7,8-diol in mouse skin in vivo.

Animals↗
PubMed1990

Insect immunity: expression of the two major inducible antibacterial peptides, defensin and diptericin, in Phormia terranovae.

Injections of low doses of bacteria into larvae of Phormia terranovae induce the appearance of potent bactericidal peptides in the blood, among which predominate the anti-Gram positive insect defensins and the anti-Gram negative diptericins. Insect defensins show significant homologies to mammalian (including human) microbicidal peptides present in polymorphonuclear leukocytes and macrophages. We report the molecular cloning of cDNAs and primer extension studies which indicate that insect defensin is produced as a prepro-peptide yielding mature defensin A (40 residues) after cleavage of a putative signal peptide (23 residues) and a prosequence (34 residues). Previous studies have established that diptericin (82 residues) is matured from a pre-peptide by cleavage of a putative signal peptide (19 residues) and C-terminal amidation. Using oligonucleotide probes complementary to the sequences of the mRNAs for defensin and diptericin, we show by in situ hybridization that both antibacterial peptides are concomitantly synthesized by the same cells: thrombocytoids, a specialized blood cell type, and adipocytes. Transcriptional studies based on hybridization of RNAs to cDNAs of defensin and diptericin indicate that the transcription of both genes is induced regardless of the nature of the stimulus (injection of Gram positive or Gram negative bacteria, lipopolysaccharides). Even a sterile injury applied to axenically raised larvae is efficient in inducing the transcription of both genes suggesting that the local disruption of the integument aspecifically initiates a signalling mechanism which the thrombocytoids and the adipocytes are able to interpret. The transcription of immune genes is relatively short lived and a second challenge yields a response similar to that of the first stimulus, indicating that the experimental insects do not keep a 'memory' of their first injection.

Amino Acid Sequence↗
PubMed1990

Immunopathology of experimental Brucella abortus strain 19 infection of the genitalia of bulls.

Antibody responses in serum and semen, and immunoglobulin containing cell (ICC) populations in the genitalia of bulls were compared after inoculating Brucella abortus strain 19 into the seminal vesicles of two bulls (ISV route) and into testes in two other bulls (IT route). Bulls seroconverted as early as 1 week post-infection (PI). Peak serum titres as determined by the serum agglutination test (SAT), complement fixation test (CFT) and ELISA occurred at PI weeks 3, 4 and 5 respectively. Highest titres were in IT inoculated bulls. Seminal antibodies against B. arbotus S19 were demonstrated from 2 weeks PI by both the SAT and the Rose Bengal Test (RBT) and highest titres occurred at PI weeks 3 and 4. Examination of immunoglobulins (Ig) in semen, however, revealed no significant differences of Ig isotypes between infected and control animals at any examination time. When bulls were killed at 7 weeks PI, quantitation of ICC in genital sections stained by the peroxidase-anti-peroxidase method revealed an overwhelming predominance of IgG containing cells in inflamed organs. In all cases IgG1- and IgG2-containing cells were prevalent, and present in approximately equal numbers. IgA-containing cells were second in prevalence in inflamed tissues while IgM cells were always in low percentage. High prevalence of ICC in infected genitalia, associated with elevated specific seminal antibodies but not with increased seminal Ig indicates that most Ig remains localised in tissues and is not transferred into genital secretions.

Animals↗