Spontaneous Regression of Induced Mammary Tumours in Rats

Abstract

MAMMARY gland tumours can be readily induced in rats by intragastric instillation of a chemical carcinogen (Shay, Aegerter, Gruenstein and Komarov, 1949; Dao and Sutherland, 1959; Huggins, Briziarelli and Sutton, 1959). It has been shown that a proportion of these tumours stop growing and some regress spontaneously (Young, Cowan and Sutherland, 1963). The purpose of this paper is to describe in greater detail the " natural history ", histology and hormone responsiveness of tumours which behave in this way. It is based on a study of 181 tumours which have been induced in 86 rats. MATERIAL AND METHODSNon-inbred female rats, descended from stock imported from Sprague-Dawley of Madison, Wisconsin, and bred commercially in Great Britain, were used throughout. They were maintained on diet G.R.25 with water ad libitum. At 50 ± 1 days of age they were given intragastrically 50 mg. 9,10-dimethyl-1,2-benzanthracene (DMBA) dissolved in 2 ml. of corn oil. This was the only dose of carcinogen to be given.Starting 4 weeks after the carcinogen, each rat was examined twice weekly for tumours. These were measured with calipers in two diameters at right angles to one another, one of which was the long axis of the tumour. The arithmetic mean of these two measurements was used as the measure of tumour size.Oophorectomy was carried out through a single mid-dorsal incision. Oestradiol-17,/ and progesterone were given together, subcutaneously, dissolved in corn oil. The doses were: oestradiol-17,/ 2 ,ag. and progesterone 8 mg., in 0-4 ml. oil, or oestradiol-17,/ 1 ,tg. and progesterone 4 mg., in 02 ml. oil. Bovine growth hormone 0.5 mg. in 1 ml. saline, and cortisone acetate 10 mg., were given subcutaneously. All hormones were given daily, 6 days a week for 3 or 4 weeks.Intercurrent infection or the development of progressively growing tumours caused us to kill most of the animals before they were a year old. Survivors were killed 1 year after giving the carcinogen when the experiments were discontinued.Portions of tumour were fixed primarily in 4 per cent neutral buffered formaldehyde for frozen sections, and fixed secondarily in formol-sublimate, or primarily in Bouin for paraffin sections, followed by haematoxylin and eosin staining.

Uptake of [3h]oestradiol by Dimethylbenzanthracene-Induced Rat Mammary Tumours Regressing Spontaneously or After Ovariectomy

“…The remainder had atrophie regions and resembled tumours which had regressed after ovariectomy, with acini lined with a single layer of flattened cells or with a large amount of fibrous stroma. A similar histological picture was found by Young & Cowan (1963). Infiltra¬ tion, mainly by lymphocytes with some plasma cells and eosinophils, was present in some degree in all the tumours but was not more marked in those regressing spon¬ taneously than in those regressing after ovariectomy.…”

Further studies on mammary tumours induced in rats by 7,12‐dimethylbenz(a)anthracene (DMBA)

“…There is no evidence that they metastasize. Invasion or infiltration of muscle has been reported by several workers (Huggins et a/., 1959;Daniel and Prichard, 1961;Young et a/., 1963) but we now believe that true invasion (Fig. 16) occurs only very rarely.…”

“…Essentially, these earliest adenomata have the same histological appearances as the adenomata which are induced by 3-MCA (Daniel and Prichard, 1961, except that a papillary structure is more frequently seen in the adenomata after DMBA. These non-secreting adenomata are clearly the tumours which have been described by other workers who have used DMBA and which have usually been described as mammary cancers or adenocarcinomata (Huggins et a/., 1961 ;Huggins and Yang, 1962;Young et al, 1963; Teller e t a / . , 1966).…”

“…In their studies on mammary tumours induced by DMBA, Young et al (1963) and Young and Cowan (1963) made the interesting observation that a large proportion of the tumours, after having attained a size of about 1.5 cm in diameter, did not expand further and that quite a number then diminished in size. A spontaneous remission of two out of 52 tumours induced by DMBA was also briefly noted by Engelbart and Gericke (1964 b).…”

“…For some years our researches have been concerned with the pituitary gland (Xuereb et al, 1954 a, b ;Prichard, 1956, 1957 a, b ; Adams et al, 1963Adams et al, b, 1964Adams et al, a, 6, 1966 and its control of growth and of the other organs of the body Prichard, 1958, 1964 d ;A d a m et al, 1963Cowie et al, 1963Cowie et al, , 1964Daniel et al, 1964 a, 6 , c). These investigations have recently included a study of the influence of the pituitary on mammary tumours induced in rats by the intragastric administration of carcinogenic hydrocarbons.…”