Biomedical subjects

A G Stead

Publications and source records attributed to A G Stead.

30 records · Page 2Linked to original sources

PubMed1986

Nitrogen dioxide exposure and lung antioxidants in ascorbic acid-deficient guinea pigs.

We have previously found that ascorbic acid (AA) deficiency in guinea pigs enhances the pulmonary toxicity of nitrogen dioxide (NO2). The present study showed that exposure to NO2 (4.8 ppm, 3 hr) significantly increased lung lavage fluid protein (a sensitive indicator of pulmonary edema) only in guinea pigs fed rabbit chow (a diet not supplemented with vitamin C) for at least 7 days, at which time lung AA was about 50% of normal. The rabbit chow diet did not cause reduced body weight as did commercial synthetic scorbutic diets, even when they were supplemented with AA. After 14 days of feeding rabbit chow, lung AA was reduced to 15% of control. At this time, alpha-tocopherol (AT) in the same lungs was reduced to 85% of control, and lung nonprotein sulfhydryls (NPSH) were increased to 114% of control. Exposure of the guinea pigs to NO2 (4.5 ppm, 16 hr) increased wet lung weight and further altered the antioxidants in deficient (but not normally fed) animals in the following manner: NPSH content was increased to 130% of control, AT was decreased to 74% of control, and AA was increased from 15 to 50% of control. These findings suggest that depletion of AA in guinea pigs removes an important defense against NO2. The lung appears to be able to partially compensate for the dietary lack of antioxidant by accumulating AA from other tissues and by increasing NPSH concentrations. However, sufficient exposure to NO2 leads to oxidation of AT and pulmonary edema. Conditions in which NO2 produced edema were accompanied by only a slight consumption of AT, and no detectable oxidation of lung AA or NPSH.

Animal Feed↗

PubMed1986

Species comparison of acute inhalation toxicity of ozone and phosgene.

A comparison of the concentration-response effects of inhaled ozone (O3) and phosgene (COCl2) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation toxicity studies. The effect of 4-h exposures to ozone at concentrations of 0.2, 0.5, 1.0, and 2.0 ppm, and to COCl2 and 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters, and mice. Lavage fluid protein (LFP) accumulation 18-20 h after exposure was used as the indicator of O3- and COCl2-induced pulmonary edema. All species had similar basal levels of LFP (250-350 mg/ml) when a volume of saline that approximated the total lung capacity was used to lavage the collapsed lungs. Ozone effects were most marked in guinea pigs, which showed significant effects at 0.2 ppm and above. Mice, hamsters, and rats showed effects at 1.0 ppm O3 and above, while rabbits responded only at 2.0 ppm O3. Phosgene similarly affected mice, hamsters, and rats at 0.2 ppm and above, while guinea pigs and rabbits were affected at 0.5 ppm and above. Percent recovery of lavage fluid varied significantly between species, guinea pigs having lower recovery than other species with both gases. Lavage fluid recovery was lower following exposure to higher levels of O3 but not COCl2. Results of this study indicate that significant species differences are seen in the response to low levels of O3 and COCl2. These differences do not appear to be related in a simple manner to body weight.

Animals↗

PubMed1986

Temperature regulation in the mouse and hamster exposed to microwaves in hot environments.

Colonic temperature was measured in naive BALB/c mice and golden hamsters immediately following 90-min exposures to 2450-MHz radiofrequency (RF) radiation at an ambient temperature (Ta) of 32.2 or 35 degrees C (dry air). Exposures were performed in a temperature-controlled waveguide which permitted continuous monitoring of the specific absorption rate (SAR) of RF energy. At a Ta of 32.2 degrees C the threshold SAR for elevating colonic temperature and the SAR resulting in a 0.5 degree C elevation in colonic temperature were, respectively, 4.3 and 6.5 W/kg for the mouse and 0.68 and 1.1 W/kg for the hamster. At a Ta of 35 degrees C these values were 0.12 and 0.63 W/kg for the mouse and 0.46 and 0.8 W/kg for the hamster. The SARs required to elevate body temperature in the mouse and hamster at these relatively warm Ta's are considerably lower than those required at cooler Ta's of 20 to 30 degrees C. Overall, the hamster became hyperthermic at lower SARs than the mouse. Ta's of 35 degrees C and greater are frequently encountered during heat waves in the summer months. Under such stressful environmental conditions where heat loss is impaired, absorption of RF radiation at relatively low SARs may lead to significant hyperthermia which would otherwise be readily dissipated at lower Ta's.

Animals↗

PubMed1986

Tumorigenesis and genotoxicity of ethyl carbamate and vinyl carbamate in rodent cells.

Vinyl carbamate (VC) is a suspect metabolic intermediate in ethyl carbamate (EC) carcinogenesis. In the present studies, EC and VC were evaluated for their relative abilities to induce adenomas and sister chromatid exchanges (SCEs) in lung cells of A/J, C3HeB/FeJ, and C57BL/6J strain mice. For both end points, animals were administered a single i.p. injection of the test chemical. Percentage of mice with adenomas and number of adenomas per mouse were compared among the three strains 24 weeks following exposure to EC or VC. Although the relative order of strain sensitivity was the same for both chemicals: A/J greater than C57BL/6J greater than C3HeB/FeJ, VC was much more potent than EC. For SCE analysis of primary lung cells cultured from treated animals, EC and VC showed potency differences similar to those observed for tumorigenesis. All three mouse strains revealed significant dose-dependent increases in SCE frequency. However, there was no strain specificity for this effect. SCE persistence over time was also compared in treated A/J and C57BL/6J mice. Although EC- and VC-induced SCE frequencies declined over a 2-week observation period, again, there was no strain specificity for this effect. VC was also tested for enhancement of SA7 virus transformation of Syrian hamster embryo cells. Significant concentration-dependent increases in cell transformation frequency were observed.

Animals↗

PubMed1986

Effect of nickel and cadmium chloride on autonomic and behavioral thermoregulation in mice.

Male BALB/c mice were injected intraperitoneally (i.p.) with nickel chloride (0, 5, 10, and 15 mg/kg) or cadmium chloride (0, 2, 4, and 6 mg/kg) and preferred ambient temperature (Ta) and activity were measured. Both metals caused marked reductions in preferred Ta and activity within 30 min postinjection. Preferred Ta and activity were depressed for up to 90 min. In a second experiment, body temperature was measured 60 min following the injection of nickel or cadmium chloride at a Ta of 20, 30, or 35 degrees C. Nickel and cadmium caused large reductions in body temperature when injected at a Ta of 20 and 30 degrees C but produced either no effect or only a slight elevation in body temperature at a Ta of 35 degrees C. In a third experiment, metabolic rate was measured continuously for 60 min following an i.p. injection of a relatively large dose of nickel (15 mg/kg) or cadmium chloride (6 mg/kg) at a Ta of 20, 30, and 35 degrees C. Both metals caused significant reductions in metabolic rate at TaS of 20 and 30 degrees C. At a Ta of 35 degrees C, cadmium caused a slight inhibition in metabolic rate while nickel had insignificant effects. These data indicate that nickel and cadmium chloride injected i.p. produce hypothermia by reducing metabolic rate and the preferred Ta.

Animals↗

PubMed1985

Effect of ozone on serum lipids and lipoproteins in the rat.

Exposure of male rats to 0 (air), 1, 1.75, and 3 ppm ozone (O3) 5 hr/day for a total of 10 days resulted in a positive linear relationship between ozone concentration and the concentrations of serum total lipoprotein free cholesterol (FCh) and high-density lipoprotein total cholesterol (HDL-Ch). The latter response was reflected in both its free (HDL-FCh) and esterified (HDL-ChE) components. On the other hand, serum triglycerides (TG) showed a marked decreasing linear trend with increasing ozone concentration. As judged by decreased body weights with no accompanying differences in feed consumption, apparent metabolic rate increased as ozone concentration increased. In another experiment, male rats were exposed 5 hr/day to either air or 1 ppm O3 for a total of 15 days. Groups of animals from each exposure were sampled at times ranging from immediately after to 44 hr postexposure. In agreement with the concentration response study, effects of O3 included increases in serum total cholesterol (Ch), HDL-Ch and HDL-FCh, and a decrease in TG. In addition, the degree of effects appeared to be maintained over the 44-hr period and to be greater than that observed at 1 ppm O3 in the concentration-response study.

Animals↗

PubMed1985

Lethality in mice and rats exposed to 2450 MHz circularly polarized microwaves as a function of exposure duration and environmental factors.

Adult male CD-1 mice and CD rats were used to determine LD50/24 h lethality rates from exposure to 2450-MHz circularly polarized microwaves. Groups of 16 mice or six rats were exposed in each of 32 combinations of nominal power density (10, 25, 50 or 75 mW cm-2), exposure duration (1 or 4 h), and environmental temperature (20 or 30 degrees C) and relative humidity (35 or 80%). An analysis of variance probit model was used to determine the influence each variable had on the probability of death. Significant factors in lethality were nominal power density, exposure duration and environmental temperature, but not environmental relative humidity. The estimated power density (mW cm-2) required to kill 50% of the animals in 24 h is halved when the environmental temperature is increased from 20 to 30 degrees C. Similarly, only 20-25% of the power density is required when the exposure duration is increased from 1 to 4 h. The use of nominal power density as a predictor of the probability of death was more efficient than specific absorption rate estimated experimentally by twin-well calorimetry. The exposure of one mouse at a time, instead of 16, did not alter the predicted death rate.

Animals↗

PubMed1985

Thermoregulation in mice following acute chlordimeform administration.

CBA/J mice were injected intraperitoneally (i.p.) with the formamidine insecticide chlordimeform (CDM) while colonic temperature, preferred ambient temperature (Ta), and lethality were monitored. In the first experiment there was a dose-dependent decrease in colonic temperature when measured 60 min after administering CDM doses of 0, 15, 30, 60, and 75 mg/kg. The hypothermic effect of CDM was more pronounced at a Ta of 20 degrees C than at 30 degrees C. In the second experiment, CDM at doses greater than 30 mg/kg caused a dose-dependent reduction in preferred Ta from the normal value of approx. 30 degrees C to approx. 22 degrees C. Thus, the CDM-treated mouse lowered body temperature by selecting a cool Ta which accelerated the hypothermic effect. In the final experiment, a 90 mg/kg i.p. injection of CDM (the approximate LD50 dose) caused 10% and 0% mortality at a Ta of 20 and 30 degrees C, respectively, and 80% mortality at a Ta of 35 degrees C. It is concluded that the physiological and behavioral response to CDM administration, i.e., selecting a cool Ta and lowering body temperature, may be beneficial to survival.

Amidines↗

PubMed1985

Comparison of lung antioxidant levels in humans and laboratory animals.

Basal lung concentrations of ascorbic acid (AA), nonprotein sulfhydryls (NPSH), and alpha-tocopherol (alpha-T) were determined in rabbits, guinea pigs, rats, hamsters, mice, domestic pigs and sheep, and in human lung samples obtained from cancer surgery patients. Significant differences were found among the laboratory animals: AA levels ranged from 25.6 mg% (mg/100 g wet weight) in hamsters to 41.7 mg% in mice, NPSH from 50.9 mg% in rats to 84.7 mg% in rabbits, and alpha-T from 1.01 mg% in hamsters to 2.74 mg% in rats. Porcine lung AA and NPSH concentrations approximated those of the laboratory animals and their alpha-T levels were the highest of all species studied. Sheep lung AA levels were comparable to those in the other species, although their NPSH and alpha-T levels appeared to be lower. Human lung concentrations of NPSH (5.2 mg%) and alpha-T (0.85 mg%) appeared low, whereas the mean AA concentration (22.1 mg%) was similar to that of laboratory animals. A partial correlation was found between AA and alpha-T levels and between NPSH and alpha-T levels in the 5 laboratory animal species.

Adult↗

PubMed1981

Modeling the Ames test.

Despite the value and widespread use of the Ames test, little attention has been focused on standardizing quantitative methods of analyzing these data. In this paper, a realistic and statistically tractable model is developed for the evaluation of Ames-type data. The model assumes revertant colony formation at any dose follows a Poisson process, while the mean number of revertants per plate is a nonlinear function of up to 4 parameters. An exponential decay term can be included in the model to adjust for toxicity. The resultant system of nonlinear equations is solved using a modified Gauss-Newton iterative scheme to obtain maximum likelihood estimates of the model parameters. Significance of the key parameters is tested by fitting reduced models and using likelihood ratio tests. The model's performance is demonstrated on data from organic extracts of various environmental contaminants. Among the advantages of the proposed model are (1) no data is discarded in the parameter estimation process, (2) no arbitrary constants need to be added to zero counts or doses, and (3) no mathematical transformation of the data is required.

Mathematics↗

PubMedDate not supplied

An analysis by chemical class of Salmonella mutagenicity tests as predictors of animal carcinogenicity.

For a number of years, investigators have recognized that humans potentially are exposed to large numbers of genotoxicants. Many efforts have attempted to validate various short-term bioassays for use as rapid, inexpensive screens for genotoxicants--especially carcinogens. In this analysis, we examine Salmonella mutagenicity as an indicator of potential carcinogenicity by comparing published (and when possible, evaluated) Salmonella results with the evaluated Gene-Tox animal carcinogen data base. The Salmonella bioassay does especially well in those cases where the level of evidence for carcinogenicity is the strongest. Analysis shows that except for specific classes of compounds, the plate-incorporation protocol and the preincubation protocol are equally efficient at detecting mutagens. This paper also demonstrates how validation values (sensitivity, specificity, etc.) vary with chemical class. Overall, this analysis demonstrates that when used and interpreted in a meaningful chemical class context, the Salmonella bioassay remains extremely useful in identifying potential animal carcinogens.

Animals↗

PubMedDate not supplied

Effect of alcohol on behavioral and autonomic thermoregulation in mice.

Male, BALB/c mice were injected intraperitoneally with ethyl alcohol (ethanol) in dosages of 0, 0.03, 0.1, 0.3, 1.0, or 3.0 g/kg and then placed in a temperature gradient which permitted the measurement of preferred ambient temperature (Ta). The 3 g/kg dosage of ethanol resulted in a slight, but statistically equivocal, lowering of the preferred Ta during the first 30 min of placement in the gradient. A replication of this experiment using a higher sample size indicated that a 3 g/kg dosage of alcohol caused a statistically significant decrease in preferred Ta. In another experiment, BALB/c mice were treated with the aforementioned ethanol dosages while metabolic rate (MR), evaporative water loss (EWL), and colonic temperature were measured 60 min postinjection at Ta's of 20, 30, and 35 degrees C. At a Ta of 20 degrees C a dosage of 3 g/kg caused a significant decrease in MR, EWL, and colonic temperature. At a Ta of 30 degrees C this same dosage caused significant reduction in colonic temperature, however; at a Ta of 35 degrees C ethanol had no effect on these parameters. In conclusion, mice treated with a relatively large dose of ethanol will select a significantly cooler Ta, which is associated with hypothermia. These combined behavioral and autonomic thermoregulatory effects suggest that ethanol led to a decrease in the set-point body temperature.

Animals↗