摘要:

Immunosuppression of humoral and cellular responses following chronic oral exposure to 1, 5, 10, and 20 ppm N‐nitrosodimethylamine (NDMA) was examined in CD‐1 mice. Monitoring of cumulative mortality and the incidence of peritoneal ascites in animals showed an NDMA dose‐related mortality and hepatotoxicity. No visible changes in immunological parameters were noted at the 1 ppm NDMA dose. Immunosuppression of immunoglobulin M (IgM) antibody response by NDMA to sheep red blood cells (SRBC) was time‐related, dose‐related, and could be reversed within 30 d by removal of the chemical from the drinking water. Cellular immune response, monitored by allogeneic stimulation of cells in mixed lymphocyte reaction (MLR), was markedly suppressed by 10 and 20 ppm NDMA. Thus, chronic exposure to NDMA, except for the low‐hepatotoxic doses of nitrosamine, resulted in a marked and persistent immunosuppression of cellular and humoral responses in CD‐1 mice. In conclusion, chronic exposure to the hepatotoxic (ascite‐inducing) doses of NDMA suppressed humoral and cellular immunity. The persistant immunosuppression could be reversed after the removal of NDMA from the drinking water. Although no direct NDMA‐related cancer was reported in humans, our data point to a potential epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression.

ISSN:0098-4108    

DOI:10.1080/15287399209531676

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Birds are useful indicators of environmental contamination because they are relatively large, conspicuous, top predators in food chains. However, concentrations of contaminants in a bird's tissues reflect the bird's exposure over wide temporal and spatial scales. Birds are most useful as monitors of exposure when these scales are known. In this paper we report concentrations of lead, cadmium, mercury, and selenium in breast feathers of common terns (Sterna hirundo) and roseate terns (S. dougallii) trapped during incubation at breeding colonies in New York and Massachusetts. Terns arrived on the breeding grounds with breast feathers grown on their wintering grounds, and regrew certain feathers that were plucked for analysis. The regrown feathers were themselves plucked, and both sets of feathers were analyzed. For roseate terns at Cedar Beach and common terns at both sites there was a significant increase in mercury levels in the feathers grown on the breeding grounds compared to those grown on the wintering ground. The differences in mercury were far greater at Bird Island than at Cedar Beach. Selenium levels at Cedar Beach were higher for the regrown feathers than the initial feathers for roseate terns, but not for common terns. Lead and cadmium levels were not significantly different at either site for either species. These results suggest that terns are exposed to significantly higher levels of mercury in the northeastern United States than they are in the wintering grounds in South America.

ISSN:0098-4108    

DOI:10.1080/15287399209531677

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

The objectives of this study were to determine the disposition of Therminol 66 in rats and to determine the effects of this heat‐transfer fluid on liver and kidney microsomal drug‐metabolizing enzymes. Therminol 66 was administered to male Sprague‐Dawley rats at various doses as either a single oral administration at 0, 100, or 300 mg/kg, or as a single 6‐h inhalation exposure at 0 or 350 mg/m3. Animals were killed 48 h after gavage or after termination of inhalation exposure. Additional groups of animals were exposed to Therminol 66 via the diet at 0, 100, 500, or 5000 ppm for 14 d, or via repeated inhalation exposure at 0, 25, 250, or 1200 mg/m3for 6 h/d for 14 d. These exposure scenarios represent approximately equivalent doses of Therminol 66 by the different routes of administration. No change in body weight was observed after acute oral or inhalation exposure, and little change in body weight was observed in animals administered Therminol 66 via the diet except at the highest dose. There was no change in kidney weight, and liver weights were increased only at the higher doses of Therminol 66. The body weight gain of animals exposed to Therminol 66 via inhalation decreased in a dose‐dependent manner over the 2‐wk exposure period. Results from the disposition study indicated that Therminol 66 did not appear to accumulate in the tissues examined and did not appear to be extensively absorbed after a single oral dose of 300 mg/kg. The whole‐body elimination half‐life was approximately 14 h and occurred primarily via the feces. There was no significant induction of hepatic aryl hydrocarbon hydroxylase (AHH) activity after single oral or inhalation exposures to Therminol 66. Ethoxycoumarin O‐deethylase (ECOD) was significantly induced only in animals exposed to 350 mg/m3via inhalation. Repeated dietary and inhalation exposures resulted in AHH and ECOD induction only at the highest doses, and the kidney appeared to be less sensitive than the liver. Animals exposed via inhalation demonstrated a greater hepatic inductive effect than did animals exposed via the diet, which may be due to absorption differences. In summary, approximately 30% of an oral dose of Therminol 66 was absorbed from the gastrointestinal tract, there was little accumulation in tissues, and the whole‐body half‐life was approximately 14 h. Induction of drug‐metabolizing enzymes was evident only at the two highest doses, and the liver was more sensitive to the enzyme inducing effects than was the kidney. ECOD activity was affected to a greater extent than was AHH activity, and inhalation produced a greater effect than did dietary exposure.

ISSN:0098-4108    

DOI:10.1080/15287399209531678

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Respirable‐sized quartz, a well‐established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid‐coated dusts were incubated for periods of 2–72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral‐specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed.

ISSN:0098-4108    

DOI:10.1080/15287399209531679

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

Inhibition of lysyl oxidase (protein‐lysine 6‐oxidase, EC 1.4.3.13) decreases the rate of collagen and elastin cross‐link formation and produces osteolathyrism in animals. Organic nitriles, including ß‐aminopropionitrile (BAPN), have been shown to irreversibly inhibit lysyl oxidase in vitro. Both BAPN and 3,3'‐iminodipropionitrile (IDPN) have been shown to produce osteolathyric changes when administered to animals. To date compounds that have been reported to inhibit this enzyme possess a primary amine functional group. In this study a series of primary and substituted aminopropionitriles was studied for their ability to inhibit lysyl oxidase activity both in vitro and in vivo. Our results show that of the compounds tested, BAPN was the most potent inhibitor of the enzyme. Reversible inhibition of lysyl oxidase in vitro was found with two secondary aminonitriles, IDPN and monomethy‐laminopropionitrile (MMAPN). There was no inhibition of enzyme activity associated with the tertiary compound 3,3'‐dimethylaminopropionitrile (DMAPN) or propionitrile, a compound lacking an amine functional group. IDPN was found to produce a slight irreversible inhibition of the enzyme both in vitro and in vivo. Pretreatment of rats with pargyline, an inhibitor of monoamine oxidase, was found to increase the inhibitory potential of BAPN (p < .1). Pargyline pretreatment did not alter the inhibitory potential for any of the other aminonitriles tested. These results suggest that the presence of a primary amino functional group is not a strict requirement for inhibition of lysyl oxidase. In addition, reversible and irreversible mechanisms of inhibition may be involved in the production of osteolathyric changes associated with IDPN exposure.

ISSN:0098-4108    

DOI:10.1080/15287399209531680

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

The biologic impact of consecutive exposures to two environmental pollutants was examined in mice exposed to silica crystals (SI) by intratracheal (IT) injection followed by an inhalation exposure to nitrogen dioxide (NO2). C57Bl/6 mice received an IT injection of 2 mg SI or sterile saline (SAL) followed by a 2‐h inhalation exposure to NO2at 20 ppm either within 2 h of or 24 h after SI instillation. During acute inflammation (d 3 postsilica), mice exposed to NO2at either time showed a dramatic and significant reduction in the number of lavaged alveolar neutrophils (PMN) when compared to silical air‐exposed mice. Animals exposed to NO224 h after silica also evidenced significant decreases in levels of lavage albumin and lactate dehydrogenase (LDH) 3 d after silica, as well as significant decreases in hydroxyproline content of the lung 30 and 60 d postsilica injection when compared to silicalair‐exposed animals. NO2administration 24 h after silica appeared to shift the appearance of PMN in the lung from d 3 to d 14, but did not otherwise alter chronic cellular inflammation. These data suggest that the marked neutrophil response and collagen deposition induced by SI can be modulated by NO2exposure and that the time of oxidant gas exposure after silica administration is critical to this modulation.

ISSN:0098-4108    

DOI:10.1080/15287399209531681

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

It has been reported previously that radioactivity derived from iodine distributes differently in the Sprague‐Dawley rat depending on the chemical form administered (Thrall and Bull, 1990). In the present communication we report the differential distribution of radioactivity derived from iodine (l2) and iodide (l−) into blood components. Twice as much radioiodine is in the form of l−in the plasma of animals treated with125I−compared to125l2‐treated rats. No l2could be detected in the plasma. With an increase in dose, increasing amounts of radioactivity derived from125l2‐treated animals distribute to whole blood compared to equivalent doses of725/−, reaching a maxima at a dose of 15.8 μmol I/kg body weight. Most of the radioactivity derived from l2associates with serum proteins and lipids, in particular with albumin and cholesteryl iodide. These data indicate a differential distribution of radioactivity depending on whether it is administered as iodide or iodine. This is inconsistent with the commonly held view that iodine (l2) is reduced to iodide (l−before it is absorbed systemically from the gastrointestinal tract.

ISSN:0098-4108    

DOI:10.1080/15287399209531682

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

In the present study, we investigated (1) whether airway responsiveness to inhaled histamine‐aerosol could be induced during 7‐d exposure of guinea pigs to 4 ppm NO2and, if so, (2) whether thromboxane A2may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n ‐ 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl(SRaw after inhalation of 0.9% NaCI), were 1.07 ± 0.20, 1.30 ± 0.20, and 1.01 ± 0.18 mM for the 3 groups later given NO2for 1, 3, and 7 d, respectively. Following exposure to NO2for 1, 3, or 7 d, EC200His values were 1.42 ± 0.25, 0.66 ± 0.10 (p < .05), and 1.05 ± 0.22 mM, respectively. These results show that 7‐d exposure to 4 ppm NO2induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long‐term exposure, and (2) thromboxane A2may play an important role in this transient airway hyperresponsiveness.

ISSN:0098-4108    

DOI:10.1080/15287399209531683

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

摘要:

PESTICIDES, CHEMICALS AND HEALTH British Medical Association, Ed. Hodder and Stoughton Publishers, Kent, England, 1992. 215 pp., £16.95 (British pounds)

ISSN:0098-4108    

DOI:10.1080/15287399209531684

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399209531675

出版商:Taylor & Francis Group    

年代:1992

数据来源: Taylor