Normally, only very small amounts of ingested aluminium are absorbed and accumulated. Despite the percutaneous absorption of many drugs and chemicals, the skin has not been considered as a possible site at which aluminium could enter the body. Application of low aqueous concentrations of aluminium chloride (A1C1(3), 6H20) (0.025-0.1 micrograms/cm2) to healthy shaved Swiss mouse skin for 130 days led to a significant increase in urine, serum and whole brain aluminium, especially in the hippocampus, compared to control animals. This percutaneous uptake and accumulation of aluminium in the brain was greater than that caused by dietary exposure to 2.3 micrograms per day in feed and water. In vitro studies demonstrated the passage of aluminium through viable mouse skin. This study shows for the first time that aluminium is absorbed through the skin of mice in vivo and this contributes to a greater body burden than does oral uptake.

Okadaic acid (OA), a diarrhetic shellfish toxin is a potent promoter of tumours in mouse skin and a specific inhibitor of protein phosphatases 1 and 2A. Recently it has been shown that OA inhibited protein synthesis in a cell-free system, with 50% inhibitory concentration of 6.3610712 M but the mechanism whereby this inhibition is mediated was still unclear. In the present study, the effect of OA on protein synthesis in Vero cell cultures was investigated. Protein synthesis was inhibited by OA alone in Vero cells in a concentration-dependent manner (IC50=27 ng/ml i.e. 3.361078 M). Since OA also induced lipid peroxidation and likely oxygen reactive radicals, it was interesting to know whether these radicals impair the protein synthesis process. Therefore, SOD+catalase known as scavenger of active oxygen radicals were added in the culture medium in the presence of OA and labelled leucine. These enzymes partially prevented the inhibition of protein synthesis induced by OA, indicating that the formation of high reactive oxygen free radicals could be one of the pathways this marine toxin induces its toxicity. Since the prevention by SOD+catalase was only partial (the IC50 increased from 27 ng/ml to 48 ng/ml i.e. 3.361078 M to 5.961078 M)itwas speculated that the production of oxygen reactive radical scavengered by SOD+catalase is not the main mechanism whereby OA induces its cytotoxicity. Vitamins E and C completely prevent the lipid peroxidation induced by OA in cells, but failed to reduce the inhibition of protein synthesis to the same level, indicating that a more specific mechanism might be responsible for protein synthesis inhibition. That is the hyperphosphorylation of elongation factor EF-2 in the protein synthesis machinery. However our results pointed to lipid peroxidation being a precocious phenomenon following the OA exposure, since a concentrationwithenhancedMDAproductionwaslower than that inducing significant cellular protein synthesis inhibition.

Aluminium is present in tap water, antiperspirants and cosmetics up to 20%. Teratogenicity of aluminium was clearly identified after per os or intravenous administra tion. Malformations and other alterations by aluminium intoxication were evaluated in fetus. In the present study, we investigated the possible transplacental passage of aluminium and its accumulation in the tissue after cutaneous uptake. Female Swiss mice received alumi nium chloride by cutaneous way (0.4 μg/day) during 20 days of gestation. The samples were assayed for alumi nium quantification by graphite furnace atomic absorp tion with Zeeman correction. This treatment led to an increase of aluminium in maternal and fetus samples (serum, amniotic fluid and organs) as compared to controls.

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Conidiospore germlings of Neuvospova crassa submitted to a heat shock at 4S'C accumulate trehalose and degrade glycogen. The opposite occurs upon reincubation at a physiologic temperature (30°C). These observations suggest a temperaturedependent mechanism for the preferential synthesis of one or the other sugar reserve. Here we show that concomitant with these shifts of temperature, occurred reversible changes in the activities of glycogen synthase and phosphorylase. Glycogen synthase was inactivated at 45'C while phosphorylase was activated. The reverse was true when the cells were shifted back to 3O'C. Addition of cycloheximide did not prevent the reversible enzymatic changes, which remained stable after gel filtration. Apparently, the effects of temperature shifts occurred at the level of reversible covalent enzymatic modifications. Trebalose-6-phosphate synthase properties were also affected by temperature. For instance, the enzyme was less sensitive to in vitro inhibition by inorganic phosphate at 50°C than at 3O'C. Fructose-6-phosphate partially relieved the inhibitory effect of phosphate at 30°C but not at 5072. These effects of the assay temperature, inorganic phosphate, and fructose-6-phosphate, on trehalose-6-phosphate synthase activity, were more evident for crude extracts obtained from heat-shocked cells. Altogether, these results may contribute to explain the preferential accumulation of trehalose 45°C or that of glycogen at 30°C.