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Based on recent findings described in accompanying reports as well as on relevant observations in the literature we hypothesize that: (1) the fundamental elements in the mechanism of the formation of "dark" (argyrophilic) neurons are independent of the causative conditions including post-mortem or in vivo mechanical injuries and various in vivo pathometabolic processes such as blood recirculation following ischemia; (2) the causative conditions, each in its own mechanical or metabolic way, induce the same morphopathological damage at one point only within each affected neuron; (3) this damage spreads throughout the respective somato-dendritic or axonal domain and entails type III argyrophilia; (4) the intraneuronal spread of the morphopathological damage consumes mechanical energy stored by the neurofilaments in the form of a metastable inner structure, and (5) is propagated by a process working, in certain structural and energetical respects, on the domino principle; and (6) the primary neuronal damage caused in the above manner might be secondarily modified in different directions by different postcausation conditions.

Objectives-To investigate whether DNA damage increased in subjects possibly exposed to high amounts of antineoplastic agents. Methods-The level of genetic damage was determined in peripheral mononuclear blood cells with the sister chromatid exchange test, the alkaline elution technique, and the cytokinesis block micronucleus test. Results-The supposed increased exposure of the study subjects was caused by a malfunction of a safety hood resulting in leakage of air during preparation of an infusion of an antineoplastic drug. Two months after a new safety hood was installed, the frequencies of micronuclei and sister chromatid exchanges of exposed nurses (n=10) were still significantly increased when compared with a matched control group (p<0.01 and p<0.05, one sided Wilcoxon test, respectively). In a second examination seven months later, the frequency of micronuclei had significantly decreased to control values (p<0.05, one sided Wilcoxon test, n=6). Moreover, the study subjects who smoked (n=8) had significantly increased frequencies of micronuclei and sister chromatid exchanges (p<0.01 and p<0.05, one sided U test, respectively). No diVerences in the rate of DNA damage could be detected with the alkaline elution technique. Conclusions-Control measures on the level of biological eVect should be performed regularly to ensure maximum safety precautions for workers potentially exposed to genotoxic agents.

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