Influence of food intake and sexual segregation on longevity, organ weights and the incidence of non-neoplastic and neoplastic diseases in rats.

In a small-scale experiment the effects of four variables were investigated in male and female Wistar rats fed on a standard laboratory chow and not deliberately exposed to any carcinogen. The variables investigated were (i) diet restriction by limiting access to food to 6.5 hr/day instead of 24 hr/day; (ii) housing males in a single-sex room as distinct from a mixed-sex room; (iii) life-long segregation of males from females, as distinct from access to one virgin female for 5 days during each alternate week; and (iv) uniparity in females versus life-long virginity. The endpoints compared were body-weight gain, longevity, visible and palpable swellings, absolute and relative organ weights, microscopically confirmed malignant neoplasms that contributed to death before the end of the study at 2 yr, incidence of other neoplasms in decedents and rats killed at the end of the study, and the incidence of various non-neoplastic conditions including myocardial inflammation and fibrosis, chronic progressive nephropathy, liver glycogen storage and fatty degeneration, mammary gland hyperplasia and secretory activity, pancreatic polyarteritis, radiculoneuropathy and certain testicular changes. The results indicated major beneficial effects of dietary restriction on most of the endpoints. By comparison the other variables had only marginal effects. Leydig-cell hyperplasia and neoplasia occurred at significantly higher incidences in males housed intermittently with females than in permanently segregated males. No convincing differences were seen between females that littered once and those that remained virgins. The relevance of these findings to the prediction of cancer mortality risk in man and to the design of rodent carcinogenicity studies is discussed.

Pathology of the forestomach in rats treated for 1 year with a new histamine H2-receptor antagonist, SK&F 93479 trihydrochloride.

The new long acting histamine H2-receptor antagonist was administered to rats at doses of 1000, 200 and 40 mg/kg body weight. Forestomach lesions of marked focal hyperplasia and hyperkeratosis were observed at a 48% incidence after 1 year daily gavage dosing with 1000 mg/kg. Lesions of this type were not seen in mid- and low-dose groups. The basal epithelium was convoluted and showed frequent mitotic figures. Two cases (4%) showed hyperplastic epithelium penetrating the muscularis mucosae. Recovery high-dose animals left untreated for a further 20-22 weeks were examined by endoscopy and necropsy and showed the hyperplasia and associated hyperkeratosis to be reversible. As penetration of the muscularis mucosae was only present in two cases at 1 year, the reversibility of this stage could not be assessed and the significance of the lesion will be determined by the results of a 2 year carcinogenicity study.