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A study of rhabdomyosarcomas induced by nickel sulphide in rats. Capstick, Valerie

Abstract

The study of rhabdomyosarcomas induced by nickel sulphide was undertaken in order to investigate their growth and responsiveness characteristics and to evaluate their possible usefulness as experimental tumour systems. A study was also made on the carcinogenic specificity of nickel sulphide. Intramuscular injections of 0.5 to 20 mg. of Ni₃S₂ resulted in tumours after two to six months, which grew fairly rapidly, once palpable. On transplantation they proved to be highly malignant, causing 100 per cent takes within approximately two weeks and death of the host within three to eight weeks. Detailed histological study was performed on many sections of tumour and muscle in order to establish identity of the rhabdomyosarcomas and to observe such cytological phenomena as muscle degeneration, tissue disruption and development of anaplasia. The carcinogenic activity of Ni₃S₂ was emphasized by the rapidity of tumour induction observed after very low doses, while the difference in latent periods suggested some correlation between dose and response. Injections of Ni₃S₂ into body organs illustrated the extreme toxicity of the substance in individual tissues. Although results were somewhat inconclusive within the time limit of the experiment, the general tenor of the data suggested that Ni₃S₂ had a toxic rather than tumourigenic action on most tissues. The appearance of rhabdomyosarcomas when the compound was in contact with abdominal or leg musculature gave evidence that nickel sulphide might have some specificity for striated muscle. Preliminary experiments with NiS indicated that its carcinogenicity, if any, was considerably less than that of Ni₃S₂, with different solubility in muscle being a possible explanation. Several of the induced tumours were used for metabolic and experimental therapy studies with various compounds. Numerous experiments indicated that the tumour was essentially unreliable for such studies since growth rates and response were not reproducible in different tumour generations. However, some general trends were noted. Response to the corticoids ranged from residual to complete inhibition of many tumours during the period of treatment with Cortisol or cortisone. Subcutaneous injections of testosterone showed acceleration of growth in some tumour lines. Tests with the Vinca alkaloids suggested some correlation with clinical anti-tumour effects, indicating an increased effectiveness of both Vinblastine and Vincristine when administered during the first week after transplantation.

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