CADMIUM IN THE PLANARIAN: NEUROTOXICITY, CARCINOGENESIS, MITOCHONDRIOGENESIS, AND ENZYME ACTIVITY.

摘要

Cadmium accumulation in the environment is a problem of increasing medical concern. The freshwater planarian displays a variety of histological, physiological, and biochemical attributes which present an attractive model system for the study of comparative and predictive toxicology. Four major categories of cadmium toxicity: Neurotoxicity, Carcinogenesis, Mitochondriogenesis, and Enzyme Activity were selected for investigation to ascertain the degree of correspondence between the planarian system and the toxicologically vulnerable systems of the phyletically higher animals.;Carcinogenesis experiments utilizing cadmium and the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) revealed that the planarian displays the major phenomenology of mammalian cocarcinogenesis, involving initiation and promotion in the progression of neoplastic disease. The histopathology, cellular characteristics, and stem cell dynamics of a potentially lethal, transplantable tumor (malignant reticuloma) was characterized and discussed in terms of mammalian neoplastic stem cell diseases.;The biogenesis of mitochondria was studied with electron microscopy in normal neoblasts and in malignant reticuloma cells which happened to display a fortuitous hyperplasia of the organelle. These studies provided strong morphological evidence for the formation of mitochondria de novo by a novel form of nucleocytoplasmic interaction; a finding which remains diametrically opposed to the prevailing theories of the origin of the mitochondrion.;The localization of magnesium-dependent Na/K-ATPase was demonstrated with histochemical techniques in a variety of planarian cell types. The ATPase complex was further characterized in terms of sensitivity to ouabain and to cadmium on the microvilli of epidermal cells. The enzyme activity was found to be significantly inhibited by cadmium sulfate; an effect which increased with the duration of exposure.;Dose-response relationships, in terms of lethality, revealed the sensitivity of the planarian to aquatic concentrations of cadium sulfate; however, the pronounced suppression of asexual reproduction (fissioning) and the occurrence of head resorption, both considered to be representative of neurotoxicity, proved to be somewhat more sensitive indicators. The effect of cadmium on cephalic serotonin and it major metabolites was investigated utilizing high-performance liquid chromatography with electrochemical detection. The result was a significant increase solely in the level of 5-hydroxyindoleacetic acid; a finding which indicates an increase in serotonin turnover and/or a decrease in excretory acid transport.