A SINGLE injection of testosterone given to female rats in their early post-natal life results in permanent morphological and functional changes of the gonadotrophin-ovarian axis. The ovaries remain small and though they contain follicles of various sizes, these do not rupture or produce any corpora lutea. Because of the lack of ovulation, these androgenised rats are permanently sterile, and there is a constant cornification of the vaginal epithelium. The luteinizing hormone content of the pituitary is decreased (Barraclough, 1961 ; Gorski and Barraclough, 1962; Jacobsohn, 1964;Swanson and van der Werff ten Bosch, 1964; Kovaics, 1965).As has been shown by Huggins, Grand and Brillantes (1961), Huggins and Yang (1962) and other authors (Dao, 1962; Young, Cowan and Sutherland, 1963;Daniel and Prichard, 1964) the intragastric administration of 9,10-dimethyl-1,2-benzanthracene (DMBA) to normal female rats results in the development of mammary tumours in a very high percentage of animals within a few months. The present study is concerned with a comparison of the carcinogenic effect of oral administration of DMBA in androgenised and in non-androgenised rats.
METHODSAndrogenisation was induced when the rats were 1 to 2 days old by a single subcutaneous injection of 2-5 mg. testosterone propionate (Neo-Hombreol, Organon) dissolved in 041 ml. oil. When the rats were between 45 and 55 days old, DMBA dissolved in corn oil was administered orally through a gastric tube (a soft rubber urethral catheter). The dose of DMBA will be mentioned later. The animals were carefully palpated for mammary tumours at weekly intervals; a tumour was recorded only when a nodule at least the size of a small pea could be felt. The animals bearing the tumours died or were killed at various times up to 8 months. The tables show only the number of rats with tumours; the number and size of the tumours is not presented as these parameters would not provide valid comparisons. The animals were killed with ether and autopsied as soon as possible. The tumours and the various organs were fixed in formol-saline and embedded in paraffin. Sections at 5 It were stained with haematoxylin and eosin.
RESULTSExperiment I.-This experiment was carried out on two groups (non-androgenised and androgenised) of female rats of the Wistar strain. A single oral dose of