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Sulindac, a non-steroidal anti-inflammatory drug, has been reported to lead to tumour regression in cases of human polyposis coli. We have investigated the effects of this drug on the growth of 1,2-dimethylhydrazine (DMH)-induced mouse colonic tumours. In one experiment, DMH and oral sulindac were administered concurrently to a group of mice for a period of up to 24 weeks, while a control group of animals received DMH only for the same period. Sulindac caused a significant reduction in both the number of mice with colonic tumours and the number of tumours per mouse. In a second experiment, two groups of mice which had already been treated with DMH for 17 weeks received either sulindac or not for 78 days. In this experiment sulindac had no effect. These results demonstrate that sulindac has a protective effect against the chemical induction of colonic tumours in mice, but does not cause the regression of established tumours.

Administration of dimethylhydrazine (DMH) to adult rats by two subcutaneous injections each of 120 mg(base)/kg body weight and spaced 10 days apart resulted in the development of renal tumours in over 90 per cent. of treated animals at 30 weeks after injection. The tumours were frequently bilateral and multiple, and had the structure of the "mesenchymal" tumours which occur in a high incidence following treatment with nitrosamines. The incidence of tumours both in the small intestine and in the colon was lower than that experienced using a weekly DMH treatment schedule.

This paper describes the progressive effects of severe copper depletion on pancreatic weight, structure, amylase content and responses to secretin and caerulein, as well as a number of general body parameters (appearance, body weight and blood indices). Copper depletion was produced by feeding young rats a copper-deficient diet alone or together with either of the two chelating agents D-penicillamine or triethylene tetramine (Trien). After 6 weeks, the copper-deficient diet alone had relatively little effect on general body parameters but reduced gland weight and the secretory response to caerulein. Addition of .D-penicillamine had a deleterious effect on general body parameters; it caused total acinar cell atrophy but left ductal and islet tissue relatively intact; gland weight was markedly reduced, and gland amylase was reduced virtually to zero; and the secretory response to caerulein was almost abolished while that to secretin was reduced. The effects of Trien on general body parameters were less severe; the secretory response to secretin was also less affected, while acinar cell atrophy, gland amylase and the secretory response to caerulein were affected to the same extent as with D-penicillamine. The effects of severe copper depletion on the pancreas were largely irreversible after 13 weeks on a copper-supplemented diet.

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