摘要:

Nicotine and the minor tobacco alkaloids give rise to tobacco‐specificN‐nitrosamines (TSNA) during tobacco processing and during smoking. Chemical‐analytical studies led to the identification of seven TSNA In smokeless tobacco (≤25 μg/g) and In mainstream smoke of cigarettes (1.3 μg TSNA/cigarette). Indoor air polluted by tobacco smoke may contain up to 24 pg/L of TSNA. In mice, rats, and hamsters, three TSNA,N’‐nitrosonornicotine (NNN), 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), and 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL), are powerful carcinogens; two TSNA are moderately active as carcinogens; and two TSNA appear not to be carcinogenic. The TSNA are procarcinogens, agents that require metabolic activation. The active forms of the carcinogenic TSNA react with cellular components, including DNA, and with hemoglobin (Hb). The Hb adducts in chewers and smokers serve as blomarkers for the uptake and metabolic activation of carcinogenic TSNA and the urinary excretion of NNAL as free alcohol and as glucuronide for the uptake of TSNA. The review presents evidence that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increased risk of lung cancer, especially pulmonary adenocarcinoma, in smokers. The high incidence of cancer of the upper digestive tract especially among men on the Indian subcontinent has been causally associated with chewing of betel quid mixed with tobacco. In addition to the TSNA, the betel quid chewers are exposed to fourN‐nitrosamines that are formed during chewing from the Areca alkaloids, two of theseN‐nitrosamines are carcinogens. The article also reviews approaches toward the reduction of the carcinogenic potency of smokeless tobacco, betel quid‐tobacco mixtures, and cigarette smoke. Although the safest way to reduce the risk for tobacco‐related cancers is to refrain from chewing and smoking, modifications of smokeless tobacco and of cigarettes are indicated to lead to less toxic products. Another more recent approach for reducing the carcinogenic effect of tobacco products is the application of chemopreventive agents, primarily of micronutrients. Future aspects in tobacco carcinogenesis, especially as it relates to TSNA, are expected in the field of molecular biochemistry and in blomarker studies, with the goal of identifying those tobacco and betel quid chewers and tobacco smokers who are at especially high risk for cancer.

ISSN:0098-4108    

DOI:10.1080/15287399409531825

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Polybrominated dibenzo‐p‐dioxins and dibenzofurans have been identified as potential environmental contaminants. The present studies were designed to characterize the chemical disposition of a tetrabrominated dibenzofuran. The isomer‐specific pattern of 1,2,7,8‐tetrabromodibenzofuran (TBDF) was chemically characterized using high‐pressure liquid chromatography, gas chromatography/mass spectrometry, infrared absorption, and proton nuclear magnetic resonance techniques. The absorption, distribution, and elimination of 1,2,7,8‐[4,6‐3H]‐TBDF were examined in the rat following a single oral, dermal, or intravenous dose of 1 nmol/kg. The 1,2,7,8‐TBDF was rapidly excreted in the bile (∼50% of the dose in 8 h). Likewise, over half of the administered dose was found in the feces and intestine contents 24 h after iv administration and in feces 72 h after oral administration. Thus, the half‐life of 1,2,7,8‐TBDF is approximately 1 d. Major tissue depots included the liver, adipose tissue, and skin. The decline in hepatic concentrations observed in the iv and bile studies occurred in conjunction with metabolic elimination as well as a slight accumulation in adipose tissue. Dermal absorption of 1,2,7,8‐TBDF, quantified as the amount contained in tissues (excluding the skin site) and excreta at 72 h, was estimated to be 29% of the administered dose. Thus, the general disposition profile of 1,2,7,8‐TBDF in the rat is similar to that of other polyhalogenated aromatic hydrocarbons. Due to its rapid elimination, which is consistent with its predicted susceptibility to metabolic elimination, acute exposure to 1,2,7,8‐TBDF would not be expected to result in the degree of toxicity associated with other more persistent congeners.

ISSN:0098-4108    

DOI:10.1080/15287399409531826

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

We attempted to develop a rodent model that exhibits characteristics of human methanol toxicities such as acidosis and visual dysfunction, which are correlated with an accumulation of formate, a toxic metabolite of methanol. Initially three groups of Long‐Evans rats with different levels of liver folate were prepared and examined for formate accumulation after methanol administration (3.5 g/kg). The folate‐reduced (FR) rats prepared by feeding a folate‐deficient diet with 1% succinylsulfathiazole yielded blood formate levels equivalent to those found in methanol‐intoxicated humans and developed signs of the visual system toxicity (a manuscript on the latter aspect is in preparation). Responses of FR rats to a variety of methanol exposure scenarios were then investigated, and the results were compared with those reported in the literature for monkeys. Formate accumulation and/or lethality were used as toxic parameters for this comparative evaluation. In FR rats dosed orally with 3 g/kg, the blood formate concentration was 9.2 mmol/L at 24 h postadministration and increased to 15.6 mmol/L at 48 h. The same dose given to monkeys yielded a plateau of 7.4 mmol/L at 12 h after methanol administration, and stayed at this level for an additional 12 h. The area under the concentration vs. time curve for blood formate in FR rats was 2.5‐fold greater than that in monkeys when 2.0 g/kg methanol was administered. After a 6‐h exposure to 1200 ppm and 2000 ppm methanol, the blood formate concentrations in FR rats were increased by 370% and 636% above the endogenous level, respectively. However, blood formate did not accumulate above the endogenous level when monkeys were exposed to methanol up to 2000 ppm for 6 h. Under acute inhalation exposure conditions, FR rats exposed to 3000 ppm methanol, 20 h/d, could not survive more than 4 d. On the other hand, monkeys exposed to 3000 ppm, 21 h/d, outlived 20 d. Moreover, monkeys survived for more than 4 d even after an exposure to 10,000 ppm. Thus, these results indicate that FR rats are more sensitive to methanol challenges than monkeys, and suggest that the FR rat could be a congruous animal model for evaluating the health effects of methanol in humans.

ISSN:0098-4108    

DOI:10.1080/15287399409531827

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Fifty‐five Yu‐Cheng (oil‐disease) children born between 1978 and 1985 to mothers who ate PCB‐contaminated rice oil in 1978–1979 were studied and compared to age‐ and sex‐matched control subjects in 1991. The children's growth profiles, bone mineral density and soft tissue composition, joint laxity, and serum parathyroid hormone, vitamin D, calcium, alkaline phosphatase, and phosphate were compared. The Yu‐Cheng children were 3.1 cm (p< .05) smaller and had less total lean mass and soft tissue mass as compared to the matched control subjects. All other parameters studied were similar in both groups. The shorter height and decreased total lean mass and soft tissue content were only seen in the Yu‐Cheng children who were the first born after the ingestion, but not in subsequent children. This was most likely due to decreased body burdens of the PCBs and related contaminants over time in the mothers.

ISSN:0098-4108    

DOI:10.1080/15287399409531828

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

The popliteal lymph node (PLN) assay has been proposed as a tool to predict in rodents those xenobiotics likely to induce autoimmune reactions in humans. To further validate this assay and to study the mechanisms involved, histologic changes in PLNs from rats injected with streptozotocin, diphenylhydantoin, pure acetone, or 50% ethanol were compared to a local graft‐versus‐host (GvH) reaction. This study suggests that routine histology of PLNs is instrumental to discard primary irritants. In addition, the hypothesis of a CvH‐like mechanism in positive PLN responses is supported by the finding that the reference compounds streptozotocin and diphenylhydantoin produced histologic changes similar to a “true” local GvH reaction.

ISSN:0098-4108    

DOI:10.1080/15287399409531829

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

During growth and development, young children are periodically exposed to relatively high concentrations of various air contaminants, including tobacco smoke and environmental pollutants generated by fossil fuel use. The effects of these exposures on respiratory function and lung development are difficult to determine because of interindividual variation and lack of accurate dosimetry. To provide information on the effects of chronic exposure to a common indoor and outdoor pollutant during lung development, a study was performed to assess the effects of exposure to two concentrations of nitrogen dioxide (NO2; 0.5 or 10 ppm) on tracer particle clearance from the airways of ferrets exposed during postnatal respiratory tract development. Separate groups of ferrets were exposed nose‐only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15 wk. Those animals exposed for 8 wk were subsequently housed in a filtered air environment until the particle clearance measurements commenced at 3 wk prior to the end of the 15‐wk exposure protocol. Radiolabeled (51Cr) tracer particles were deposited in the respiratory tract of all animals by inhalation, and the clearance rates from the head and thoracic regions were separately monitored for 18 d. No significant effects of the NO2exposure on head airways clearance were seen. In contrast, the rates of particle clearance from the thorax of both the 8‐ and 15‐wk groups exposed to 10 ppm NO2were significantly reduced, and did not differ from each other. Thoracic clearance was also reduced in animals exposed to 0.5 ppm, but the rate was not significantly different from that of the clean air exposed controls. These results show that NO2at moderate concentrations caused highly significant changes in the deep lung of the juvenile ferret, and suggest that impairment of the clearance function may be only slowly recovered after chronic exposure.

ISSN:0098-4108    

DOI:10.1080/15287399409531830

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

A crab apple clone (Malus brevipes1021), highly resistant to the apple maggot, is being used in breeding programs developing commercial apple cultivars. This study has discovered that this crab apple contains a natural cholinesterase (ChE) inhibitor that caused a 77.5% in vitro inhibition of rat blood ChE activity. This crab apple also showed a relatively high total (titratable) acidity of 1.28%. The commercial, nonresistant, apple cultivar McIntosh was capable of causing a 7.9% inhibition of blood ChE in vitro. The total acidity in Mclntosh was 0.45%. A 4‐wk feeding study compared 2 groups of 5‐wk‐old Fischer 344 male rats fed diets containing 45% of either M. brevipes or Mclntosh freeze‐dried apples to a third (control) group of rats fed a semipurified diet. In vivo blood ChE activities were similar in all groups of rats, as well as hemoglobin, hematocrit, and red blood cell counts. The liver mixed‐function oxidase activity through aminopyrine U‐demethylase in the rats fed the apple diets was higher than the controls, but p‐nitroanisoleO‐demethylase activity was induced only in the animals fed the maggot‐resistant crab apple. Lowered growth with concomitant lowered food intake, in the otherwise healthy rats fed the maggot‐resistant crab apple diet, was attributed to the less palatable, highly acidic fruit. This study indicates that the natural ChE inhibitor in the insect‐resistant appleM. brevipesis apparently detoxified upon ingestion.

ISSN:0098-4108    

DOI:10.1080/15287399409531831

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399409531832

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399409531824

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor