THE carcinogenic properties of iron macromolecular complexes in rats and mice were described in 1959 and the early 1960's (Richmond, 1959; Haddow and Horning, 1960;Baker et al., 1961; Lundin, 1961;Fielding, 1962). Since that time, a number of iron-containing compounds have been tested and found to induce subcutaneous tumours in various experimental animals (see Roe, 1967 Twenty animals received 17 weekly subcutaneous injections of ferric sodium gluconate in the right flank-0' 1 ml. for the first 3 weeks and 0.05 ml. for the following 14 weeks. The total amount of iron injected was 75 mg. Twenty untreated mice served as controls.The animals were examined daily. Sick mice were killed and the survivors were killed 16 to 18 months after the beginning of the experiment. Complete post-mortem examinations were carried out and tissues showing macroscopic abnormalities were fixed in Bouin's solution. Paraffin sections 5 ,u thick were prepared and stained with haematoxylin and eosin. RESULTSThe survival of mice in the test and control groups, together with the incidence of local and distant tumours, is shown in Table I. Injection-site tumours developed in 5 test animals-the first after 10 months and the last after 15 months. Once palpable, they grew rapidly and it was necessary to kill the mice within 30 days of the first appearance of a definite subcutaneous mass. The morphology of these neoplasms was similar to that reported previously in animals injected with iron-preparations. All of them were spindle cell or pleomorphic sarcomas,
IT was reported in 1964 that rats which received repeated subcutaneous injections of cadmium-precipitated ferritin developed sarcomas at the site of injection, interstitial cell (Leydig cell) tumours of the testes and testicular atrophy (Haddow, Roe, Dukes and Mitchley, 1964;Roe, Dukes, Cameron, Pugh and Mitchley, 1964). Previous and parallel observations demonstrated that simple inorganic cadmium salts were carcinogenic-both at the site of injection (Kazantzis, 1963;Haddow et al., 1964) and in the testis (Parizek and Zahor, 1956; Meek, 1959;Kar and Das, 1960;Gunn, Gould and Anderson, 1963)-and it thus seemed likely that some or all of the effects of cadmium-precipitated ferritin were due to its content of cadmium. To confirm this hypothesis, cadmium-free ferritin was tested for carcinogenic activity in rats and mice. MATERIALS AND METHODSExperiments were carried out on 48 male CB Wistar rats and on 64 male CB stock mice. The rats, which were 6 weeks old at the beginning of the experiment, were divided into test and control groups, each consisting of 24 animals. The mice, 11 weeks old, were divided into a test group of 24 animals and an untreated control group of 40 animals. The rats and mice were housed in metal cages and maintained on cubed Diet No. 86 (Messrs. Dixon, Ltd., Ware, Herts.) and water ad libitum.
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