Tumours of the respiratory tract in rats and hamsters following chronic inhalation of engine exhaust emissions.

The potential carcinogenic effect of inhaled automobile exhaust emissions was examined in rodents. Both rats and hamsters were exposed to the emissions from (1) a gasoline engine, (2) a gasoline engine fitted with a three-way catalytic converter, (3) a diesel engine and (4) a diesel engine with particle filtration. Exposures were for 16 hours per day, 5 days per week, for 2 years. All hamsters were sacrificed at the end of the 2-year exposure period, whereas the rats surviving after 2 years of exposure were maintained for a further 6-month observation period without additional exposure to emissions. Some of the hamsters in each treatment group were pretreated with diethylnitrosamine to induce respiratory tract tumours. No statistically significant changes were seen in the incidence of respiratory tract tumours in emission-exposed hamsters compared to controls. This lack of a treatment-related effect was seen in both the nitrosamine pretreated and the non-pretreated hamsters. There was no increase in the incidence of lung tumours in rats exposed to filtered diesel exhaust or to the exhaust from the gasoline or gasoline-catalyst engines. There was a statistically significant increase in the incidence of lung tumours in rats exposed to diesel engine emissions compared to controls. A clear dose response was evident in both males and females, although the incidence of lung tumours was markedly higher in females (96% in rats surviving beyond 2 years) than in males (44% in rats surviving beyond 2 years). An increased incidence of lung tumours was observed only in rats exposed to mean concentrations of diesel soot particles of either 2200 or 6600 micrograms/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemoglobin adducts in animals exposed to gasoline and diesel exhausts. 1. Alkenes.

Blood samples from rats and hamsters exposed to automotive engine exhausts in the Committee of Common Market Automobile Constructors long-term inhalation study at Battelle-Geneva were analysed for the levels of 2-hydroxyethylvaline (HOEtVal) and 2-hydroxypropylvaline (HOPrVal) in hemoglobin (Hb). These adducts to the N-terminus of the Hb chains were determined by gas chromatography-mass spectrometry of derivatives obtained by a modified Edman degradation that specifically cleaves off alkylated N-terminal amino acids (valine in Hb). The adduct levels found correspond to the metabolic conversion of about 5-10% of inhaled ethene and propene to ethylene oxide and propylene oxide, respectively, in agreement with results from earlier studies on mice inhaling radio-labelled alkenes. It is concluded that the alkenes, via epoxides, are the main sources of the observed HOEtVal and HOPrVal. From calculated doses and estimates of genotoxic potency the contribution from ethene in urban air to human cancer risk is discussed.

A scanning tunneling microscope (STM) for biological applications: design and performance.

The design of a scanning tunneling microscope (STM) for biological applications, operating at ambient pressure, is described. The STM is combined with an "auxiliary" light microscope to facilitate finding and identifying specimen areas of interest. The performance of the STM has been tested with evaporated gold films and with graphite. We have evaluated evaporated carbon and platinum/carbon films deposited on glass or mica to be used as specimen supports. First applications to biological material coated with a conducting film of platinum/carbon are described.

Pulmonary function of the green sea turtle, Chelonia mydas.

Lung volumes, oxygen uptake (VO2), end-tidal PO2, and PCO2, diffusing capacity of the lungs for CO (DLCO), pulmonary blood flow (QL) and respiratory frequency were measured in the green sea turtle (Chelonia mydas) (49-127 kg body wt). Mean lung volume (VL) determined from helium dilution was 57 ml/kg and physiological dead space volume (VD) was about 3.6 ml/kg. QL, determined from acetylene uptake during rebreathing, increased in proportion to VO2 with temperature. Therefore, constant O2 content difference was maintained between pulmonary arterial and venous blood. DLCO, measured using a rebreathing technique, was 0.04 ml X kg-1 X min-1 X Torr-1 at 25 degrees C. Several cardiopulmonary characteristics in C. mydas are advantageous to diving: large tidal volume relative to functional residual capacity promotes fast exchange of the alveolar gas when the turtle surfaces for breathing: and the concomitant rise of pulmonary blood flow and O2 uptake with temperature assures efficient O2 transport regardless of wide temperature variations encountered during migrations.

On-line data acquisition and control in a physiology laboratory.

A series of programs are described for use in estimating the pulmonary function of laboratory animals. Data acquisition and control are through a Hewlett-Packard (HP) 1000-F minicomputer. The system allows the estimation of respiratory parameters similar to those obtained in laboratories estimating pulmonary function in humans.

Diffusion-limited gas exchange across amphibian skin.

Cutaneous gas exchange function of amphibians is conveniently analyzed in lungless salamanders in which all gas exchange is through the skin. Measurements in Desmognathus fuscus (Plethodontidae) have yielded the following results: 1) Cutaneous transfer of O2 and CO2 is limited predominantly by diffusion. 2) Accordingly, in environmental hypoxia, O2 uptake decreases. 3) Anaerobiosis contributes to energy balance during the first few hours of hypoxia only. Thereafter unknown biochemical adjustments take place that allow the animal to restore metabolite levels characteristic of normoxia regardless of the continued reduced oxygen uptake.

Anaerobic energy metabolism during severe hypoxia in the lungless salamander Desmognathus fuscus (Plethodontidae).

In the lungless salamander Desmognathus fuscus, mean body weight 4.5 g, the changes in total body concentration of adenosine triphosphate (ATP), creatine phosphate (CP) and lactate (LA) were measured during exposure to a severely hypoxic atmosphere (PO2 = 25 Torr) for 48 h at 13 degrees C. ATP and CP decreased, reaching a minimum at 3 h of exposure, and LA increased, attaining maximum values after 12 to 24 h of hypoxia. Thereafter recovery was observed and control values of ATP, CP and LA were reached after 48 h of sustained hypoxia. This behavior is attributed to a biochemical adjustment to hypoxia of the metabolic machinery which leads to normalization of chemical energy stores in spite of O2 uptake being persistently reduced to 30% of its normoxic level. The anaerobic energy yield derived from splitting of ATP and CP and from LA formation corresponded to about 2/3 of the oxidative energy deficit during the first 3 h of hypoxia. Thereafter anaerobic mechanisms were responsible for insignificant contributions to the energy balance.

Kinetics of inert gas equilibration in an exclusively skin-breathing salamander, Desmognathus fuscus.

Characteristics of cutaneous gas exchange in amphibians were studied by analysis of the equilibration kinetics of an inert test gas in salamanders which have neither lungs nor gills. Specimens of the common dusky salamander (Desmognathus fuscus, Plethodontidae, Urodela), average body mass 6.1 g were equilibrated with 20% chlorodifluoromethane (Freon 22) in oxygen. The time course of subsequent elimination of Freon 22 into atmospheric air was more rapid in living than in dead animals. This difference was attributed to convective transport by blood flow. Several alternative models were proposed, providing a basis for quantitative analysis of the data. All models yielded similar values for convective conductance due to blood flow. In order to calculate blood flow therefrom, a simplified circulation model based on anatomical evidence was used: the cardiac output is in part directed to the skin, subserving gas exchange with the environment, and in part to the internal organs; the blood returning from both skin and internal organs is mixed before reaching the heart. Depending on assumptions regarding the model and the partitioning of blood flow to the skin and to internal organs, the following range of values was calculated from the experimental data: cardiac output, 85-195 mul/(min-g body mass); cutaneous blood flow, 27-63 mul/(min-g body mass). Due to inherent assumptions these values must be considered minimum estimates.