摘要:

AbstractChronic cigarette smoke exposurein vivocauses decreased conversion of [14C]arachidonic acid (AA) to prostacyclin (PGI2) by isolated aortic tissue and increased conversion to thromboxane (TXA2) by isolated platelets from rats. Alterations in the PGI2/TXA2balance may be part of the mechanism through which smoking increases the risk of cardiovascular disease. To study the influence of smoke exposure duration on this response, male rats were exposed daily to 10 puffs of freshly generated cigarette smoke. Animals were klledd after 1, 4, 14, 28 and 57 days of smoke exposure and 3, 7, 14 and 28 days after cessation of the 57‐day of smoke‐exposure regimen. Elevated carboxyhemoglobin levels during the smoke‐exposure sessions verified smoke (gas phase) inhalation. Statistically significant alterations in prostacyclin synthesis preceded those of thromboxane. A decrease of 20‐25% (P<0.05) in PGI2production from [14C]AA in isolated aortic tissue was found beginning 28 days after smoke was initiated and quickly rebounded when smoke exposure was terminated. Increased production of TXA2from [14C]AA by isolated platelets became statistically significant (P<0.05) on the 57th day and returned to normal 7–14 days after cessation of smoke exposure.To determine the effect of gas phase constituents on the PGI2/TXA2balance a second series of experiments divided male and female Sprague‐Dawley rats into sham, whole smoke and gas phase groups. Gas phase was produced by passing whole smoke through a Cambridge filter to remove particulate matter. Per cent COHb averaged 1.4 for sham, 7.8 for whole smoke and 9.4 for gas phase groups. After 8 and 12 weeks of exposure, whole smoke decreased aortic PGI2and increased platelet TXA2both in male and in female rats. In contrast to whole smoke exposure, 8 or 12 weeks of exposure to gas phase constituents filed to produce any statistically significant alteration in PGI2and TXA2formation.It was concluded that changes in PGI2and TXA2formation occur readily following initiation or termination of chronic whole smoke exposure and that substances present in the particulate phase of smoke are essential to producing th

ISSN:0260-437X    

DOI:10.1002/jat.2550060202

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractWhen rats were exposed to 2 mg l−1(˜640 ppm) of carbon dislfide (CS2) for 4 h, the concentration of free CS2in the red blood cells (RBCs) approached a plateau within 2 h. Free CS2in plasma reached a steady state concentration within 15 min of exposure. More than 90% of the free CS2in blood was found in the RBCs regardless of the length of exposure.In vitrostudies showed that about 90% of the free CS2partitioned into the RBCs regardless of whether the CS2was added first to the plasma or directly to the RBCs. Hence, it appears that the RBC is the major carrier of CS2in blood. It was found that 98% of the free CS2in red blood cell lysates was associated with hemoglobin. Free CS2in RBCs was readily partitioned into olive oil (RBCs/oil=1/6), less readily into the plasma (RBCs/plsma=12/1), and only to a small extent into phosphate buffer (RBCs/buffer=39/1). The extraction of free CS2‐loaded RBCs into albumin solution increased with increasing albumin concentrations. CS2can be extracted with buffer, protein solution, and oil, indicating that CS2in RBCs can be transferred to the medium in which the RBCs contact. It is proposed that RBCs may also play an important role in the transport of CS2from lung to tissues and vice versa. The possible role of RBCs in the transport of other organic solvents in the blood is also discu

ISSN:0260-437X    

DOI:10.1002/jat.2550060203

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractMale rats were exposed to 0.125, 0.25 or 0.5 ppm of ozone or clean air for up to 1 year. During this exposure period there was little evidence for collagen accumulation in the lungs. However, the rate of incorporation of tritriated proline into both lung collagen and total lung protein was accelerated. These data suggest that exposure to ozone under these conditions results in an increase in the turnover of collagen as well as other lung proteins.

ISSN:0260-437X    

DOI:10.1002/jat.2550060204

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractPhenobarbital was observed to produce cardiovascular malformations in embryonic chicks. Malformations included simple ventricular septal defects, ventricular septal defect associated with dextroposition of the aorta, double outlet right ventricle, and several types of aortic arch anomalies. Embryos were exposed to phenobarbital at doses of 1–25 μmol on day 4 of incubation (Hamburger‐Hamilton development stage 24). Doses equal to and greater than 5 μmol phenobarbital (26 mg/kg egg) significantly increased the frequency of embroys with cardiovascular malformations compared with lesser doses and with saline. A significant reduction in heart rate and abnormal rhythm of the heart were observed in embryros treated with teratogenic doses of phenobarbital. No arrhythmia nor significant changes in heart rate were observed in embryos exposed to subteratogenic doses of phenobarbital or to s

ISSN:0260-437X    

DOI:10.1002/jat.2550060205

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThree statistics for analysis of microtitre plate mutagenesis fluctuation tests were studied by simulation, and in enzyme‐activated assays of dimethylnitrosamine and diethylnitramine. A survival‐adjusted χ2statistic (‘Gsq’) was compared with Katz's normally distributed statistic (‘Phi’), and with the survival‐independent statistic (‘Zsq’) of Gilbert. When toxicity was either very low or high, the Phi statistic either could not be evaluated over the whole range of possible background mutant frequencies, or sometimes it indicated unusually high levels of statistical significance, even when the other tests were negative. The survival‐adjusted Gsq closely followed the Zsq statistic throughout the experimentally useful range of toxicities and mutant background values, with some improvement in sensitivity. Within the range 80 ± 10% survival approximately, Katz's statistic ‘Phi’ was the most sensitive. The choice of statistical test could affect the estimate of the minimal effective mutagenic concentration by a factor of 10–100. For screening unknowns, both types of test (Phi and Gsq (or Zsq)) may help in detecting suspect pro‐mutagens and in designing a confirmatory assay. Bacterial population statistics are needed to assess the value of s

ISSN:0260-437X    

DOI:10.1002/jat.2550060206

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractLiver S9 fractions were prepared from male and female Syrian Golden hamsters and Sprague‐Dawley rats, 1, 3, 6 and 12 months of age, which were either iuninduced (corn‐oil treated) or induced with Aroclor 1254 suspended in corn oil. These preparations were compared at varying protein levels for their ability to metabolize polycyclic aromatic hydrocarbons (benzo(a)pyrene, 3‐methylcholanthrene, 7,12‐dimethylbenzanthracene), aromatic amines (N‐2‐acetyl‐aminofluorene, β‐naphthylamine, benzidine), and nitroso compounds (N‐nitroso‐diethylamine, nitrosopyrrolidine, nitrosodiethylmethylurea) to products mutagenic toSalmonella typhimurium. With 3‐methylcholanthrene or benzo(a)pyrene in the presence of S9 preparations from Aroclor‐treated male rats, the numbers of revertant colonies decreased with increasing age of the animals. Mutagenicity of aromatic amines was not affected by the age of the donor animals from which the S9 was prepared. The use of liver S9 from 1‐month‐old hamsters produced the highest number of revertant colonies with nitrosodiethylamine. This number decreased with preparations from animals of increasing age. The greatest number of revertant colonies with nitrosopyrolidine occurred with preparations from male hamsters. A decrease in numbers of revertant colonies with increasing age was observed with the S9 preparation from Arcolor‐treated male rats. Nitroso‐diethylmethylurea was mutagenic only in the presence of S9 from male or female Aroclor‐treated hamsters and the metabolic activity of the S9 preparations did not change with age.S9 preparations from livers of 50–70‐year‐old humans were compared for their ability to produce mutagenic metabolites at a number of protein levels. Very low levels of mutagenicity with polycyclic aromatic hydrocarbons were seen with all human liver S9. Two preparations from human liver obtained shortly after death metabolized both benzidine and β‐naphthylamine (known human carcinogens) to mutagenic products. Very low or no increases in the number of revertant colonies were seen with the other human S9s. However, all of these liver S9 preparations gave a positive mutagenic response withN‐2‐acetylaminofluorene. The only nitrosamine mutagenic with human liver S9 was nitrosopyrrolidine. All of the human preparations metabolized this carcinogen at similar levels.To obtain a positive mutagenic response with a number of these compounds, it was important that the tissue samples be obtained with minimum delay after death. The ability of S9 preparations made from tissues of older rats to metabolize chemicals to mutagenic products was diminished, and compared well with the results obtained with S9s from 50–70‐year‐old humans. These findings demonstrate the value of theSalmonellamutagenicity assay used with liver S9 preparations fr

ISSN:0260-437X    

DOI:10.1002/jat.2550060207

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe efficiency of a composite oral treatment on131I thyroid uptake was investigated in three adult volunteers. The treatment consisted of 10 g of calcium alginate, 3 g ferrihexacyanoferrate(II), 130 mg of potassium iodide and 5 g of Zn‐DTPA. This mixture when administered 30 min before131I almost completely blocked the131I thyroid uptake. This indicates that simultaneous administration of other antidotal agents do not cancel or decrease the effect of potassium iodide on131I thyroid uptake. The finding deserves attention since composite oral treatment is the recommended therapy in cases of accidental environmental exposure to several radionuclide

ISSN:0260-437X    

DOI:10.1002/jat.2550060208

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractImmediately after a 20 min nose only exposure to51Cr labeled polystyrene latex microspheres (1.4 MMAD, geometric standard deviation = 1.3, 2 μg m−3), 23% of the measured radioactivity was within the trachealungs of the exposed rats, 37% was within the gastrointestinal tract, 10% was within the defurred head, and 30% was on the fur. One hour after deposition these percentages had changed to 20, 64, 5 and 11% respectively. As a result of this non‐pulmonary particle load transiting the esophagus, external thoracic radioactivity measurements did not accurately reflect excised lung measurements until 30 h post‐deposition. Consequently, it was necessary to combine excised lung ratioactivity data (0–30 h post deposition) with serial external thoracic measurements (30–934 h post‐deposition) to measure the clearance of these microspheres. Use of an annulus shaped detector sufficiently increased sensitivity to allow measurements to be made through at least 934 h post‐deposition. The lung radioactivity retention curve was biexponential with half times of 34.3 ± 2.3 and 963 ± 107 h. Simultaneous exposures to 5% CO2increased deposition by 40% but failed to reduce deposition inhomogeneity and

ISSN:0260-437X    

DOI:10.1002/jat.2550060209

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractA method for the detection of andromedotoxin in plant material and relicta from cases of poisoning due to Rhododendron and other members of the Ericacea is described. This method, which overcomes the problems associated with basing the diagnosis on the clinical signs exhibited and untrained identification of plant materials, has been successfully applied to the investigation of a number of field outbreaks of Rhododendron poisoning in animals.

ISSN:0260-437X    

DOI:10.1002/jat.2550060210

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe use of smokeless tobacco (chewing tobacco or snuff) results in contact between this material and the lining of the mouth over relatively long periods of time. As tobacco contains nicotine and a carcinogen, nitrosonornicotine (NNN) there is a likelihood of systemic absorption of both these compounds under these conditions. This study measured the penetration of nicotine and NNN across skin and various regions of oral mucosa. Specimens of porcine skin, keratinized gingiva and non‐keratinized floor of mouth and cheek mucosa were placed in perfusion chambers and the flux across these tissues of isotopically labeled water, nicotine and NNN was determined; permeability constants were calculated for each compound and for each region and the values compared statistically. Skin showed a lower permeability than the oral regions to all compounds and floor of mouth was generally the most permeable site. Nicotine passed across oral mucosa almost as rapidly as water, the most permeable region being floor of mouth, whereas gingiva and buccal mucosa showed a similar, but lower, permeability. The non‐keratinized oral carcinomas, regions with the higher permeability being sites that show the greatest tendency to develop such lesi

ISSN:0260-437X    

DOI:10.1002/jat.2550060211

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY