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Biomedical subjects

J D Adams

Publications and source records attributed to J D Adams.

At least 91 records · Page 5Linked to original sources
PubMed1987

Toxic and carcinogenic agents in dry and moist snuff.

The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

Acetone↗
PubMed1987

A study of snuff carcinogenesis.

Dry snuff contains high levels of tobacco-specific N-nitrosamines (TSNA); their concentrations exceed by more than 100 times the quantities of nitrosamines found in any other consumer product. The concentrations of TSNA are similar in dry snuff and in the more popular moist snuff. In addition to the four TSNA identified earlier [N'-nitrosonornicotine (NNN), 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosoanatabine (NAT) and N'-nitrosoanabasine (NAB)], two new nitrosamines were detected in snuff, namely 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAl; 0.07-0.15 ppm) and 4-(N-nitrosomethylamino)-4-(3-pyridyl)-1-butanol (iso-NNAl; 0.06-1.1 ppm). After oral swabbing with a mixture of NNN and NNK, rats developed tumours of the oral cavity and lung, showing that these TSNA are not only organ-specific carcinogens but can also induce local tumours. After swabbing an extract of snuff containing the same concentrations of NNN and NNK, significantly fewer tumours were induced in the oral cavity and lung, indicating inhibition of the tumorigenic activity of the TSNA by other snuff constituents.

Animals↗
PubMed1986

1-Methyl-4-phenylpyridine (MPP+) induces oxidative stress in the rodent.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces an irreversible parkinsonism in primates. Recent evidence suggests metabolism of MPTP to 1-methyl-4-phenylpyridine (MPP+) is required for toxicity. We have proposed that MPP+ may play a central role in the toxicity of MPTP, but direct assessment of the effects of MPP+ in brain is difficult. Therefore, we have sought to define the mechanism of peripheral MPP+ toxicity in the rat and mouse. Systemically administered MPP+ produced its major pathology in the lung and was typified by perivascular edema. An increase in plasma glutathione disulfide concentrations also resulted, suggesting that MPP+ in analogy to paraquat produces oxidative stress. In addition, the lethality of MPP+ in the mouse was increased by dietary selenium deficiency. These results define in both pathological and chemical terms the potent systemic toxicity of MPP+ and suggest that MPP+, because of its high concentration in primate brain, has the potential to play an important role in the CNS toxicity of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
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

The delivery and uptake of nicotine from an aerosol rod.

Nicotine aerosol rods were assessed for their possible usefulness as substitutes for cigarettes. Under standard FTC conditions, the per puff delivery of the aerosol rod averaged 0.3 micrograms nicotine/puff after 10 puffs and 6.4 micrograms nicotine/puff after 60 puffs. After puffing on the rods, no nicotine was detected in the plasma or urine of seven subjects.

Aerosols↗
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

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

Decompression sickness and intravenous bubble formation using a 7.8 psia simulated pressure-suit environment.

The purpose of this study was to determine the minimum spacesuit pressure required to prevent decompression sickness (DCS) during operational conditions in a 50% oxygen/50% nitrogen environment. In this study, 30 male volunteer subjects were exposed in groups of three, to three consecutive daily extravehicular activity (EVA) simulations at 7.8 psia (5,031 m altitude equivalent) for a continuous period of 6 h. During each altitude exposure, the subjects participated in similar exercise workloads expected to be experienced by astronauts during a typical EVA scenario. Precordial Doppler monitoring revealed that 73.3% of the subjects had intravenous bubbling during at least 1 d of the 3 d of exposure, with 26.7% remaining bubble-free during the entire study. No correlation was found between either body fat or age and incidence of bubble formation. One case of DCS occurred during the study indicating that 7.8 psia is not sufficient pressure to totally preclude DCS in a 50% oxygen/50% nitrogen environment. The necessary pressure awaits further study.

Adult↗
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↗
PubMed1985

Cadmium and nickel in mainstream particulates of cigarettes containing tobacco grown on a low-cadmium soil-sludge mixture.

Cigarettes were prepared from tobaccos grown in the greenhouse on a soil to which a low rate of a municipal sewage sludge was applied. The cigarettes were smoked by machine and the mainstream particulate fraction was analyzed for total cadmium and nickel content. Sludge-grown and control (soil-grown) tobaccos contained, respectively, 5.33 and 1.87 ppm of cadmium and 1.15 and 0.64 ppm of nickel. The average quantities of cadmium and nickel (ng/cigarette) found in the mainstream particulate fractions were, respectively, 220.5 and 78.5 for the sludge-grown and 147.4 and 72.6 for the control treatments. The difference between treatments was highly significant (p less than 0.001) for cadmium but not significant for nickel.

Cadmium↗
PubMed1985

On the pharmacokinetics of tobacco-specific N-nitrosamines in Fischer rats.

Methods were developed to determine the biological half-lives and rates of distribution and elimination of N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in the F344 rat. The formation and persistence of an in vivo equilibrium between NNK and NNAL were also studied. The method consists of extraction and elution of the nitrosamines through a Clin-Elut column with ethyl acetate, followed by concentration and analysis by a gas chromatography-thermal energy analyzer. The biological half-lives for NNN and NAT were 184 and 540 min, those for NNK and NNAL ranged from 25 to 37 and 184 to 298 min, respectively. A relatively short biological half-life for the TSNA suggests a correlation with carcinogenic potency.

Animals↗
PubMed1985

New aspects of tobacco carcinogenesis.

In tobacco smoke, catechols represent a major group of cocarcinogens. Model studies have indicated that polyphenols and polysaccharides are two major groups of precursors for the catechol formation during smoking. Results from the application of BP together with catechol on mouse skin indicate that the detoxification path of BP metabolism is decreased and the formation of the BP-7,8-diol is increased in comparison to the metabolism pattern observed when BP is applied alone. It remains to be demonstrated that the increased BP-7,8-diol formation leads also to increased formation of BP-DNA adducts in epithelial tissues. The nicotine-derived N-nitrosamines represent a major group of carcinogens in chewing tobacco, snuff, and tobacco smoke. Their concentrations in processed tobacco and smoke exceed by far those of carcinogenic nitrosamines in other environmental materials. Whereas it has been shown that nicotine gives rise to NNN and NNK during tobacco chewing, the endogenous formation of these potent carcinogens upon smoke inhalation has so far not been demonstrated. However, the formation of N-nitrosoproline in cigarette smokers and snuff dippers proves that smoke and snuff have a measurable potential for the endogenous formation of carcinogenic nitrosamines. Finally, the data presented here indicate that the individuals subjected to passive smoke exposure under controlled conditions take up measurable amounts of particulate matter. The nicotine level in the saliva of nonsmokers reflect recent passive smoke exposure and levels of nicotine and cotinine in urine reflect the long-term exposure to smoke particulates. The indicators, measured in saliva and serum, make it clear that uptake of particulates due to passive smoke exposure corresponds only to a low percentage (less than 2%) of the particulates that represent the uptake of a 1 pack-a-day adult smoker. However, in special settings, such as in the exposure of infants to the smoke pollutants generated by their mothers, uptake of smoke constituents can reach levels which raise concerns as to possible long range toxic effects. A broader base of subjects and a wider range of pollution situations need to be tested in order to substantiate the significance of the dosimetry of uptake executed to date. Such measurements constitute an attempt at more accurate risk assessment for nonsmokers in smoke polluted environments.

Animals↗