A New Strain of Mice with a High Incidence of Mammary Cancers and Enlargement of the Pituitary

Abstract

THE beneficial effects obtained by hypophysectomy in the treatment of advanced cancer of the human breast have revived interest in the role of pituitary factors in the pathogenesis of mammary tumours (Coppedge and Segaloff, 1951;Segaloff, Gordon, Horwitt, Schlosser and Murison, 1951; Scowen and Hadfield, 1955; Hadfield, 1956a and b). Many years ago experimentalists produced evidence for a promoting influence of the adenohypophysis on the growth of mammary cancers in mice. Morphological descriptions of the pituitary in this condition remain scanty and to our knowledge no pattern has emerged which could be called typical for cancer of the breast. When we came into the possession of a high mammary cancer strain, the pituitaries of which showed gross abnormalities, it was hoped that a useful tool had become available for a reinvestigation of the role of pituitary hormones in the development of tumours of the breast. In the following an account will be given of the origin of this strain (NZY), of the endocrine abnormalities observed in the females and of the neoplasms occurring in animals of both sexes. METHODS AND MATERIALThe mice were kept in thermostatically controlled rooms at a temperature 70 ± 2°F. The composition of the stock diet as well as of the food given to the breeders has been described in a previous communication (Bielschowsky and Bielschowsky, 1956).At the age of 28 days the animals were separated from their mothers and the female offspring from the male. Some of the females were kept as virgins, the others, at the age of 8 weeks, were mated to their brothers with whom they remained until they had produced and reared 4-7 litters. However, when a breeder failed to become pregnant during a period of 3 months the animal was removed from the breeding box.Forty miales, 31 virgins and 84 breeders belonging to the 18th-24th generation were kept under observation during their full life span. They were killed when they appeared to be seriously ill or when palpable tumours were discovered. Some mice with mammary cancers were allowed to live for 5-8 weeks after the tumour was first observed. It was impossible to keep a constant number of animals per box but care was taken to avoid overcrowding. The maximum nunmber of mice at any one time never exceeded 15 in boxes measuring 28 x 43 X 13 cm.The material presented in this paper consists of the 155 mice mentioned above together with 43 healthy females and 6 males killed for a study of the endocrine glands and their target organs.

The effect of methylcholanthrene and different social conditions on the appearance of breast tumours in NZY mice.

“…The present results confirm the reports of Bielschowsky et al (1956) that a high proportion of untreated NZY female mice will develop breast tumoursdespite the failure to demonstrate mammary tumour agent in the Birmingham sub-strain. Fig.…”

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AN endocrinologically interesting strain of mice (NZY) was developed in New Zealand by Dr. Marianne Bielschowsky, and described in several reports (Bielschowsky, Bielschowsky and Lindsay, 1956;Bielschowsky, 1958). The females had prolonged periods of dioestrus and it was possible to induce deciduomas in virgins by traumatization of the uterus.

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Uterine and Mammary Neoplasia and other Changes (Amyloidosis) in C₃H Mice, Related to Ovariectomy, Estrogen and Methylcholanthrene

“…The induction of mammary gland tumors by estrogen in the present expe riments is apparently related to stimulation of mammary gland tissues [5], Similar conclusions that prolactin as well as estrogen stimulate breast tu mor formation were reported recently [31]. No attempt was made in present experiments to determine the types of the circulating ovarian hormones, which may be significant in mammary carcinogenesis or a protection from it.…”

Spontaneous Auto‐Immune Disease in NZB/BL Mice

“…The NZB/BL mice belonged to a strain developed in the Cancer Research Department of the Otago University Medical School (Bielschowsky et al, 1959) and concerned animals between the 38th and 43rd generations. The crossbred animals belonged to the F1 and F2 generations of a cross between NZY/BL (Bielschowky, Bielschowsky and Lindsay, 1956) and NZB/BL animals.…”