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OESTROGENS promote keratinisation in specific organs rather than generally as does vitamin A insufficiency (Gitlin, 1957), suppress the formation of mixed carcinomas of the uterine cervix in mice (Glucksmann and Cherry, 1962), and promote differentiation in the form of keratinisation in cervical tumours of mice (Klavins and Kaufman, 1962). This enhancement of keratinisation by oestrogens might be useful in the treatment of tumours refractory to radiation which often fail to respond to treatment with increased differentiation. This may be particularly useful for the mixed carcinomas of cervix which have given very poor results for both radiotherapy and surgery. On the other hand, oestrogens stimulate proliferation of the epithelium and stroma of the female genital tract, an effect that might be harmful to the patient if produced in tumours at these sites.The effect of castration, and of additional treatments with oestrogens, progesterone and testosterones have been studied experimentally mainly on mice and have yielded results varying with strain of mice, dosage and type of carcinogen, dosage and type of solvent for the sex hormones. Prolonged administration of oestrogens is followed infrequently by cervical tumours in mice (Gardner, 1959; Murphy, 1961), but in these experiments cholesterol pellets have been used as carriers and cholesterol itself induces cancers. Oestrogen treatment causes septic pyometra which may promote tumour formation, so that oestrogenic hormones may act only indirectly as carcinogenic agents (Gardner, 1953). Administration of oestrogens in combination with chemical carcinogens neither shortens the induction period nor increases the yield of cancers in intact mice (Murphy, 1961; Klavins and Kaufman, 1962; Laffargue, Samso, Luscan and Francois, 1963; Blanzat, Hirai and Pincus, 1966). In castrate mice treated with methylcholanthrene for 4 weeks only, subsequent administration of a diethylstilboestrolcholesterol pellet has increased the production of tumours and this effect was greater for a 33 % than for a 10 % hormone content of the pellet. The greater incidence of pyometra in mice treated with a 33 % as opposed to a 10 % oestrogenic pellet may account for the higher incidence of carcinomas (Murphy, 1961). Oestrogens do not alter the yield of cancers in spayed mice given full carcinogenic treatment by the thread method or painting. Taki (1967) reports an approximately equal stimulation of cancer production in castrate mice by the additional application of cholesterol alone, oestradiol in cholesterol and oestradiol only, if the treatment and observation period is limited to 5 weeks.

CARCINOMAS and sarcomas have been induced in the salivary glands of mice, rats anid guinea-pigs by the local application of various chemical carcinogens (Rush, Baumann and Maison, 1940; Franseen, Aub and Simpson, 1941; Steiner, 1942;Bauer and Byrne, 1950; Bauer and Grand, 1954; Standish, 1957) (Bauer and Byrne, 1950; Steiner, 1942). Steiner found some carcinosarcomas especially in mice under treatment with methylcholanthrene.In all the experiments with the exception of those of Rush et al., who used corn oil as the solvent, a pellet of cholesterol or wax containing the carcinogen was implanted into the salivary glands. The initial fibrous reaction around the pellet was followed by squamous metaplasia in the adjacent epithelial tissue, the formation of epidermoid cysts and the subsequent development of squamous carcinomas in relation to the walls of the cysts. Rush et al., also found squamous metaplasia of the glandular tissue prior to malignant transformation. Steiner claims that the cells of the acini and ducts undergo metaplasia and thus contribute to tumour formation while Standish maintains that the striated ducts are the source of the carcinomas. Bauer and Byrne state that in their experiments the tumours originated from the cells of the intercalated ducts. Sarcomas probably arose from the stroma within or around the salivary glands (Steiner) or from the proliferating connective tissue around the deposited pellet (Standish). In a previous study on the carcinogenic action of ionizing radiations on the salivary glands, a sex difference was found (Glucksmann and Cherry, 1962) and this observation has led us to investigate the effect of endocrines on the carcinogenesis induced in salivary glands by chemical carcinogens, particularly in male rats, as a corollary to our studies of hormonal effects on the induced carcinogenesis in the cervix and vagina of rats and mice. The present report is concerned with the early effects of the local injection of a chemical carcinogen into the salivary glands of the rat and the histogenesis of the induced tumours.

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