Bertram D. Dinman

Non-Concept of "No-Threshold": Chemicals in the Environment

Present confusion that equates the presence of a biological effect with a deleterious implication ignores several concepts. To believe that a single molecules presence in a cell implies a definite potential for deleterious effect disregards stochastic considerations. To believe that such molecules cause an undesirable effect disregards the presence of multiplicity of interferring substances. Such thinking also does not take into account the fact that the dose of a foreign atom may be related to the probability of its interacting with an available active site, or that similar probability governs the answers to the question of whether interactions will occur at discrete topographical loci upon a structural or functional molecule (or on a possible precursor). While the construction of stochastically sound model is remote, the reasonableness of the hierachy of cellular element concentrations as these relate to metabolic function suggests that a threshold for biological activity exists within a cell at 104 atoms. The cellular organism operates within a quantitative rate limit that transcends any statements having only qualitative bases. Thus concepts concerning encroachments on response capabilities over a lifespan are inadequate descriptors of biological activity in the absence of quantitative qualifiers.

Heavy Metal Levels in Acculturated and Unacculturated Populations

In the comparison of metals in the hair, blood, and urine of 100 acculturated and 90 unacculturated individuals copper level was found to be the same in both groups. Levels of lead and cadmium were found to be markedly lower in the unacculturated population. Mercury was the same, higher, or lower in the unacculturated population, depending on sex and location. The higher values resulted from levels in men. On the basis of current knowledge, elevated levels may derive from exposure to alkyl mercury.

Acute carbon tetrachloride hepatotoxicity. V. Enzymatic activity and structural concomitants during the regenerative phase.

The general impression obtained from review of literature concerning CCI4-induced hepatotoxicity suggests that one should find a reciprocal relationship between serum enzymes and liver activity. This especially would apply if hepatocytes passively lost enzymes as a result of altered permeability or actual cellular disruption. Hepatocytes damaged by CCI4 may produce enzyme in response to injury. Whether such evolution could arise from de novo synthesis, activation of nascent enzyme, overloading of protein degradation pathways, or CCI4-induced steric rearrangements cannot be clearly determined. Regardless of the precise mechanism of enzymic elaboration, an increase in these cellular and serum catalysts could represent a homeostatic rather than retrograde response; GPT- and GOT-induced gluconeogenesis may be a compensatory response to glycogen depletion. Possible compensatory ends met by other cellular enzyme increases are not apparent al this lime.

A cellular model for studying accommodation to environmental stressors: A protective response to subtoxic exposure to cadmium

Abstract A model is described for testing the effect of exposure to subtoxic challenge upon cellular integrity. The model incorporates Physarum polycephalum as a biological assay system, the ability of the cell to traverse the cell cycle as an indicator of cell integrity, and the use of repeated challenge by cadmium ion as a mechanism for amplifying the response to subthreshold exposure. A sensitivity profile of Physarum , developed by periodic exposure to 5 × 10 −4 m Cd 2+ for 30 min throughout the cell cycle, contains two peaks of sensitivity resulting in mitotic delay, one in early S and the other in late G 2 . Physarum accommodates to a subtoxic challenge of Cd 2+ by developing a protective response: Exposure to 10 −4 m Cd 2+ for 30 min in early G 2 (0.45 cycle), which does not delay mitosis, protects Physarum against a mitotic delay of 105 min resulting from exposure to 4 × 10 −4 m Cd 2+ for 30 min in late G 2 (0.75 cycle). Protection persists for at least two cell cycles.

II. Effect of Ozone Inhalation on Nadide Phosphate Levels in Tracheal Mucosa

Epithelial cell suspensions were prepared from rat trachea by the brush technique. The ratio of reduced nadide phosphate (NADPH) to oxidized nadide phosphate (NADP+) was determined by the enzymatic cycling method. In normal rat tracheal epithelium, this ratio was greater than one. This preponderance of NADPH over NADP+ agrees with other investigators’ findings for rat liver and brain. The NADPH/NADP+ ratio in rat tracheal epithelia, following 1 hour of ozone inhalation at 33 ppm, is not significantly different from the controls. Ozone destroyed NADPH, but not NADP+, in vitro. This experiment’s potential depends upon the availability of microanalytical methods for biological compounds possibly having crucial roles in toxic mechanisms. Its usefulness in elucidating the nature of the toxic-inhalant injury may be greater in studying tracheobronchial disease than diseases primarily affecting lung parenchyma.Exposure to 33 ppM O/sub 3/ for 1 hr had no effect on the ratio of NAPD/NADPH (avg ratio about 1.34) in rats. Exposure of the two compounds in solution in vitro to bubbling 33 ppM O/sub 3/ showed a time-related significant decrease in NADPH but no effect on NADP. O/sub 3/ may be absorbed by upper-respiratory epithelium or by intracellular compounds other than NADPH.

An experimental approach to study the toxicity of nonparticulate air pollutants. I. Rationale and methods.

This report describes an experimental model for studying the toxicity of nonparticulate air pollutants, in terms of a ‘biochemical lesion.’ Changes in chemical composition of lung tissue homogenate, following inhalation of a noxious gas, could neither be traced to a particular tissue component, nor be regarded as solitary unrelated incidents. Biochemical changes in a single kind of cell, separated from the respiratory tract after the animal’s exposure to poisonous gas, may be more directly related to the toxic mechanism of the investigated gas. A technique for isolating epithelium lining the rat trachea has been adapted from a method used to separate tracheal and bronchial epithelia from human autopsy material Ozone was chosen as test gas in this experimental approach because of its importance in photochemical smog and its presence in certain industrial environments.