IN a careful examination of the long-term effects of large doses of lead, Zollinger (1953) described the tumours of the kidney in rats induced by repeated injection of lead phosphate. This finding has been confirmed by Walpole (personal communication in Matthews and Walpole, 1958) who also obtained tumours in the kidney by injection of lead phosphate. The tumours were similar to those caused by administration of 4-amino-5-fluorobiphenyl (Matthews and Walpole, 1958).Van Esch, van Genderen and Vink (1959, personal communication) fed rats on a diet containing 1 per cent of basic lead acetate over a period of two years. At the end of this period the surviving rats were killed and many were found to have malignant tumours of the kidney. That rats should survive for two years on a diet containing 1 per cent lead acetate is surprising, in view of the known toxicity of lead compounds. In this paper, the findings of van Esch, van Genderen and Vink (1959, personal communication) are confirmed. Fairhall and Miller (1941) had previously carried out experiments with much lower concentrations of lead. They maintained rats on diets containing 0.1 per cent of lead arsenate and 0-1 per cent lead carbonate for two years. The mortality in the group fed the lead carbonate was almost the same as in the controls. At the end of the two year period, the kidneys of the rats were found to have many swollen cells with large vesicular nuclei and brown granules; the latter were most prominent in the proximal convoluted tubules, but no neoplasms were reported. The concentration of lead in the kidney was higher than in the liver but lower than in bone. Lead compounds are known to cause increased excretion of porphyrins by interfering with haemoglobin metabolism. As the porphyrins pass through the kidney they might be the immediate carcinogen, rather than the administered lead. Lead is deposited in bones, so that if the lead itself were carcinogenic then bone tumours would be expected. The hypothesis that porphyrins might be the immediate carcinogens in the kidney was tested by administering allylisopropylacetylcarbamide (Sedormid), which also causes porphyrinuria, to rats. The porphyrin concentration in the urine of rats dosed with lead acetate, sedormid and other substances known to cause porphyrinuria was measured. ExperimentalTwo groups of 20 male 10-week-old Wistar rats were maintained on a 20 per cent protein diet of the following composition; white flour, 68-7 per cent ; casein, 11-5 per cent; milk powder, 8 per cent; margarine, 3*3 per cent; chalk, 1-3 per cent; salt mixture (Glaxo Laboratories), 0 8 per cent; " Bemax ", 2 5 per cent;
IN the course of a series of tests of iroii-containing compounds and irolicomplexes for carcinogenicity, it was found that a preparation of rat-ferritin induced not only a high incidence of sarcomata at the site of repeated subcutaneous injection, but also testicular atrophy, Leydig-cell hyperplasia and benign Leydigcell tumours (Haddow, Dukes and Mitchley, 1961 In this paper the induction of sarcomata at the site of subcutaneous injectiol-i of " rat-ferritin " or cadmium sulphate in rats is described and the failure to induce similar tumours in mice bv injection of the same agents, reported. In an accompanying paper (Roe et al., 1964) the testicular and pituitary changes following the injection of eadmi-Lun sulphate, or ferritin. are described and discussed.MATERIALS AND ',,%IETHODS Rats : Male albino rats of the Chester Beatty straiii were used. In the first experiment courses of injection were begun when the rats were 3-4 weeks old (80-1 00 g.), and in the third experiment when they were 6-7 weeks old (I 70-200 g.).(Rats of this strain are exceptionally large.) The rats were housed in metal cages in groups of 10, fed cubed Diet 86 on 2 days of each week and white bread plus milk, cod liver oil, margarine, or marmite on the 5 other davs. Water was provided ad libitum,
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