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Biomedical subjects

D L Coffin

Publications and source records attributed to D L Coffin.

At least 19 recordsLinked to original sources

Transplantation and chromosomal analysis of cell lines derived from mesotheliomas induced in rats with erionite and UICC chrysotile asbestos.

The histological lesions, chromosomal characteristics and transplantability of 6 erionite-induced and 7 UICC chrysotile-induced rat mesotheliomas are compared. The tumours were of 4 types: tubulopapillary, fibrosarcomatous, mixed fibrosarcomatous and tubulopapillary, and mixed fibrosarcomatous and chondrosarcomatous. Cell lines derived from these tumours displayed heterogeneous chromosome anomalies, but none were unique either to chrysotile or erionite treatment. Six of 7 erionite-induced and 4 of 6 UICC chrysotile-induced tumours had various anomalies of chromosome No. 1. When 7 cell lines were transplanted into syngeneic rats, all produced tumours that were pathologically similar to the original tumour, regardless of the route of injection. Cytogenetically, the cell lines derived from tumours after intrapleural transplantation resembled the injected cell line. The cytogenetic analysis of the cell lines derived from the tumours after subcutaneous transplantation is in progress. The induction period for transplanted tumours was 28-80 days.

Aluminum Silicates

Significance of mass and number of fibers in the correlation of V79 cytotoxicity with tumorigenic potential of mineral fibers.

The cytotoxicity of four tumorigenic minerals: erionite(w), erionite(c), UICC crocidolite, UICC chrysotile and nontumorigenic mordenite was compared in Chinese hamster lung V79 cells. The results indicate that the tumorigenic minerals were toxic by showing more than 50% toxicity for at least one dose between 10 and 100 micrograms/ml. Mordenite was nontoxic. Higher potency of erionite, however, was not evident in this system when the dose considered was expressed in mass units. On the other hand, when the degree of cytotoxicity was considered per number of mineral fibers, it was clear that fewer erionite fibers of all three dimensions (A greater than or equal to 3; L greater than or equal to 8.0 micrometers, W less than or equal to 0.25 micrometer; and L less than 5.0 micrometers, W less than or equal to 0.1 micrometer) than those of UICC crocidolite and UICC chrysotile were needed to produce similar toxicity. This suggests that the dose in number of fibers may be a better parameter than the total mass dose as a correlate of tumorigenic potential.

Aluminum Silicates

Nasopharyngeal removal of ozone in rabbits and guinea pigs.

In estimating pollutant concentrations responsible for observed pulmonary effects, nasopharyngeal removal of the pollutant plays an important role. The nasopharyngeal removal of ozone (O3) in anesthetized male guinea pigs and male and female rabbits was determined by drawing O3 through the isolated upper airways at a constant flow rate which approximated the animal's respiratory minute volume. The tracheal O3 concentration in rabbits and guinea pigs was markedly similar and was linearly related to the chamber concentration of O3 over a range of 196--3920 micrograms/m3 (0.1--2.0 ppm O3). Regression analyses showed that O3 removal in the nasopharyngeal region is approximately 50% in both species. Both rabbit sexes responded similarly over the concentration range studied. Exposures of guinea pigs to O3 concentrations between 3920 and 5880 micrograms/m3 (2.0 and 3.0 ppm) showed that, at these higher concentrations, relatively more O3 is removed by the upper airways.

Animals

Influence of crystallization habit of minerals on in vitro cytotoxicity.

Four samples of cummingtonite-grunerite series in various crystallization habits were tested in vitro. The cytotoxicity to Chinese hamster ovary cells and hemolysis to sheep erythrocytes were inversely proportional to the structural faults and surface defects of the minerals. At a comparable surface area, asbestiform grunerite (UICC amosite), semi-asbestiform cummingtonite, acicular cummingtonite, and acicular grunerite were found to be cytotoxic and hemolytic in a decreasing order. The influence of particle size on hemolysis and cytotoxicity was observed with acicular grunerite. Although samples of relatively large particle size were found to be inert, samples of smaller particle size were cytotoxic as well as hemolytic. No apparent relationship between surface charge and hemolysis as well as cytotoxicity was observed.

Animals

Experimental approach to the determination of pulmonary carcinogenic influences of shale oil effluents.

Oil derived from oil shale deposits is known to contain many organic complexes. The formation of carcinogenic hydrocarbons is temperature-dependent and is associated with retorting of the oil. Furthermore, oil shale is a rich source of inorganic elements such as the metals. Biological studies have demonstrated that concentrated extract of tars from combustion of shale oil are carcingenic to the skin of mice. The purpose of the current project is to evaluate the potential carcinogenic hazard from inhalation of retort and combustion effluents for man. These studies will be carried out in pathogen-free rats by intratracheal instillation with and without added factors such supplemental particles and known carcinogens as interactants.

Animals

Influence of exposure mode on the toxicity of NO2.

Pollutant gases are subject to a variety of physical and chemical interactions within the atmosphere due to cyclic production and various meteorological influences. In consequence there is generally a diurnal concentration profile for NO2 which consists of peaks of short duration and irregular occurrence superimposed on a low background. Since this variation could play an important role in the toxic effect of NO2, the influences of various exposure modes was studied. Continuous and intermittent exposure studies were used to determine the relationship between biological response and length of exposure to various concentrations of NO2. As the concentration decreased, the slope of the regression line decreased. After adjusting for total differences in the product concentration x time, the response for the two exposure modes was essentially the same. When a constant concentration x time level was employed, a short-term exposure to a high concentration produced a greater effect than exposure to a lower concentration administered over a longer period. Using these curves, the relationship between level of effect, concentration, and time can be determined. Results of these studies indicated that the frequency and amplitude of short-term peaks are of significance even though the exposure is interrupted with periods of zero concentration of NO2.

Animals

Similarity between man and laboratory animals in regional pulmonary deposition of ozone.

Predicted pulmonary ozone (O3) dose curves obtained by model analysis of the transport and removal of O3 in the lungs of guinea pigs, rabbits, and man indicate that a general similarity exists among these species in the shapes of the dose curves. An overview of the major features of the lower airway mathematical model used is presented. This model predicts that the respiratory bronchioles receive the maximum O3 dose. For exposures corresponding to tracheal O3 concentrations greater than 100 micrograms/m3 (0.05 ppm), the predicted respiratory bronchiolar dose for rabbits was found to be twice that for guinea pigs and 80% of that for man. Sensitivity analyses are presented for model parameters relating to the treatment of the chemical reactions of O3 with the mucous layer. The role of tidal volume in the determination of pulmonary uptake of O3 in man is examined. The consistency and similarity of the dose curves for the three species lend strong support to the validity of extrapolating to man the results obtained on animals exposed to O3.

Animals

A comparative study of experimental and spontaneous emphysema.

Normal lung architecture of the rat, mouse, hamster, horse, and human was compared to that of emphysematous lungs from the same species by utilizing a light microscope and a scanning electron microscope (SEM). The results obtained by SEM examination of normal and emphysematous lungs corresponded to those obtained with the light microscope. However, the SEM provided a view of alveoli and airway morphology not obtainable with the light microscope. Because of the variability in pore size and number of pores per alveolus, a pore-to-alveolus ratio was determined with the SEM on the normal lungs of the above species plus the rabbit, dog, guinea pig, and rhesus monkey. Depending on the extent of other pathways for collateral ventilation, differences in number of pores per alveolus may affect a species' susceptibility to a given mechanism in the genesis of spontaneous or induced emphysema. The small number of pores per alveolus in the rat, mouse, rabbit, and hamster suggests that they would not be responsible for emphysematous changes. Pores do appear to be involved in human and horse emphysema.

Aged

Time--dose response for nitrogen dioxide exposure in an infectivity model system.

The concentration of NO2 in polluted atmosphere is subject to wide variation, according to peak traffic load, industrial productivity, intensity of sunlight and meteorological conditions. Normally NO2 has a low basal concentration with superimposed spikes when the above conditions are optimal for its production. Thus, it is important to determine the relative importance of a short-term, relatively high concentration of NO2 versus exposure for longer periods of minimal dose levels. This problem was approached experimentally by measuring the effect of NO2 on an animal's resistance to the induction of bacterial pneumonia. The data collected indicate that: (1) in short-term dose-response studies using the same Ct (concentration x time) product of 7, the actual concentration exerts a greater influence on NO2 effect than does the duration of exposure; (2) when concentration is held constant and the time increased, the average difference in mortality from controls can be seen after only 1 hr exposure to 3.5 ppm and after 3 weeks of exposure to 0.5 ppm; and (3) the relative mean survival time at 3.5 ppm for 1 hr was 18--36 hr less than that of the control animals.

Animals

Sulfuric acid effect on the deposition of radioactive aerosol in the respiratory tract of guinea pigs.

The effect of inhalation of sulfuric acid (H2SO4) aerosol on respiratory deposition of radiolabeled streptococcus aerosol was investigated in guinea pigs. A 60 minute exposure to 3020 mugm/m3 H2SO4 (1.8 mum CMD) resulted in a 60% greater total respiratory deposition rate than control animals and a proximal shift in the regional pattern of deposition to the nasopharynx. Dose-response experiments revelaed that a concentration of 30 mugm/m3 H2SO4 (0.25 mum CMD) also induced a proximal shift in the regional pattern of particle deposition but in this instance the shift was to the trachea. The interrelationship between mass concentration of H2SO4 and its particle size to the interpretation of these results is discussed. A hypothesis concerning the relationship of these data to previously reported respiratory physiologic effects of H2SO4 inhalation and to a pathophysiologic mechanism which may underlie effects attributed to sulfur oxides by epidemiologic studies is described.

Aerosols

Effect of trace metals on phagocytosis by alveolar macrophages.

Experiments were performed to measure the effect of trace metals on a vital function of the alveolar macrophage (AM), phagocytosis. Since certain trace metals were found to reduce the viability of AMs, a technique was developed to permit examination of live cells only for phagocytosis. Evidence is presented that Ni(2+) selectively altered the phagocytic activity of AMs at concentrations lower than those which caused cell death. It is further shown that a level of VO(3) (-) that caused extensive lysis and death did not reduce phagocytosis in surviving cells. The effects of Cd(2+), Cr(3+), and Mn(2+) on AMs were also examined.

Animals