Distribution of 64Cu in Foetal and Adult Tissues in Mice: Influence of Sodium Diethyldithiocarbamate Treatment

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Abstract
64Cu (as 64CuCl2) was given intravenously to male C57BL mice and to pregnant C57BL mice at various stages of gestation. The disposition of the 64Cu in the adult animals and in the foetuses was studied by autoradiography and δ spectrometry. The effects of treatments with diethyldithiocarbamate (DEDTC) on the disposition of the 64Cu in the animals were also examined. In addition, the ability of Cu to affect chondrogenesis was studied in an embryonic limb bud culture system. The results showed a strong uptake of 66Cu in the liver of the adult animals at all intervals (5 min.–24 hrs). At short survival intervals, there was also an uptake in the kidney cortex, the gastrointestinal mucosa, the adrenal, the pancreas, and the erythrocytes. Exposure to Cu may cause liver and kidney injuries, which may be related to the strong accumulation in these organs. 64Cu passed the placenta to the foetuses at all stages of gestation, although this occurred at a relatively slow rate. Within the foetuses the highest concentrations were found in the liver. Cu was observed to be toxic in the chick limb bud mesenchymal spot culture system although at relatively high concentrations. Foetal malformations and embryotoxicity may therefore be interpreted as a result of direct action of Cu on embryonic structures, although placental and/or maternal influence cannot be excluded. Pre– or posttreatments of the animals with DEDTC, which is a chelating agent, caused a very marked increase in the concentration of 64Cu in most tissues of the adult animals and also an increased foetal uptake of the metal. The highest relative increase was found in the brains of both the adults and the foetuses. The complex between DEDTC and Cu is lipophilic, and a facilitated penetration of the complex through the cellular membranes probably explains the increased uptake of the 64Cu in the tissues. DEDTC can induce noxious effects on the central nervous system and on foetal development. It is possible that these effects are mediated via an interference in the metabolism of metals, including Cu