The effect of restricting food intake by approximately 20% was studied in rats and mice. Both species were fed as similar "natural" diet composed chiefly of cereals and bone meal. The duration of the rat study was 24 months, but mice were studied for their whole lifespan of 36 months. In the mice, restriction increased longevity, and in both species the incidence of tumours was reduced and the onset delayed. The effect upon the different types of tumour varied; some types appeared to be unaffected by restriction, but the most common types in each species, liver tumours in mice, pituitary, mammary and skin tumours in rats, were significantly reduced.

A survey of the pathology of 567 laboratory-bred cotton-eared marmosets (Callithrix jacchus) is presented. There were few significant pathological changes in animals used in studies up to 6 months in duration, suggesting that the marmoset can be a useful non-human primate species for routine toxicology. The most common pathological changes encountered were chronic colitis, chronic thyroiditis and interstitial mononuclear infiltration in the kidney. No internal parasites were encountered, nor were any viral or bacterial diseases identified. Fungal disease was confined to a few cases of oesophageal mycoses. In a long term study a variety of pathological changes have been observed, including a 'wasting' syndrome, not related to skeletal muscle myopathy, with atrophy of the gastrointestinal tract, salivary glands and gonads, haemosiderosis and fatty change in the liver and osteoporosis. It is suggested that these changes may be related to protein deficiency and that the nutritional requirements of the marmoset require further investigation.

Tamoxifen was administered orally to neonatal rats on days 2-5 after birth and the subsequent effects on the uterus were characterized, morphometrically, over the following 12 months. Tamoxifen inhibited development of the uterus and glands in the endometrium, indicating a classical oestrogen antagonist action. Between 24 and 35 months after tamoxifen treatment there was a significant increase in the incidence (26%) of uterine adenocarcinomas and a 9% incidence of squamous cell carcinomas of the vagina/cervix in the absence of any oestrogen agonist effect in the uterus. This demonstrates that an oestrogen agonist effect is not an absolute requirement for the carcinogenic effect of tamoxifen in the reproductive tract of the rat. The unopposed oestrogen agonist effect of tamoxifen on the endometrium may not be the only factor involved in the development of endometrial cancers. It is possible that tamoxifen causes these tumours via a genotoxic mechanism similar to that seen in rat liver. However, using (32)P-post-labelling we failed to find evidence of tamoxifen-induced DNA adducts in the uterus. Tamoxifen may affect hormonal imprinting of oestrogen receptor responses in stem cells of the uterus, causing reproductive tract cancers to arise at a later time, in the same way as has been proposed for diethylstilbestrol. If these rodent data extrapolate to humans, then women who are taking tamoxifen as a chemopreventative may have an increased risk of vaginal/cervical cancer, as well as endometrial cancer.

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