The Chemical Induction of Breast Tumours in the Rat: Hormonal Factors in Tumour Production

Abstract

MAMMARY tumours in the rat can be induced by a variety of methods. These include intensive treatment with hormone preparations, e.g. growth hormone (Moon et al., 1950) and oestrogens (Geschickter, 1939; Mackenzie, 1955), by the administration of aminofluorene compounds (Bielschowsky, 1944(Bielschowsky, , 1947 Symeonidis, 1954) and by certain carcinogenic hydrocarbons. These latter substances have been administered by various routes, but the most rapid method of induction has been reported by Huggins, Briziarelli and Sutton (1959) giving methylcholanthrene daily by stomach tube, a technique originally described by Shay et al. (1949).Painting the skin of the rat with an oily solution of 9: 10-dimethyl-1: 2-benzanthracene (DMB) at fortnightly intervals is a highly effective method of inducing breast tumours. In initial experiments (Howell, 1959) it was shown that 77 per cent of female rats developed mammary tumours in an average time of 4-75 months, and furthermore, a single application of the carcinogen gave a tumour incidence of 75 per cent, although in this instance the average induction time was extended to 12 months. The present paper is concerned with the effects of gonadectomy, hormone supplements and the effects of normal and pathological lactation on tumour development following skin application of DMB. The experiments on lactation were undertaken since Marchant (1958) has shown that breast tumour development in IF mice is inhibited by full lactation, and that unilateral removal of the nipples in lactating IF mice allows the development of breast tumours on the side without nipples, but not on the normal side (Marchant, 1959). MATERIALS AND METHODS GeneralThe animals were derived from two sources; entirely outbred laboratory stock, and from the Birmingham strain (Laboratory Animals Bureau Catalogue of Uniform Strains, No. 626, 1953).In all experiments, the animals whose age at the start of carcinogenic treatment varied between 2 and 4 months were kept in galvanized wire-mesh cages, never more than 5 rats to a cage, and were given rat cube (Heygate & Sons, known as the Thompson diet) and water ad lib. Twenty drops of a 1.6 per cent solution of DMB in olive oil was applied to the skin at fortnightly intervals, 5 drops to each side of the ventral and dorsal surfaces; a single treatment averaged 1.3 ml. or 20.8 mg.DMB. After the first month of treatment all the animals were examined at fortnightly intervals to determine the presence of palpable breast tumours. When a tumour was found, treatment. was stopped and usually the animal was killed,

GH-dependent growth of experimentally induced carcinomas in vivo

“…The study was conducted in seven areas of the world, included populations that exhibited a wide range of incidence rates for breast cancer, and involved 4323 cases and 12,699 controls. Others observed that parity provided significant protection from chemically induced mammary cancer in rats (Howell 1960, Moon 1969, Moore et al 1981. We found that GH was significantly lower in parous rats compared with age-matched virgin controls, while other mammotropic hormones were not significantly altered (Thordarson et al 1995).…”

Development and characterization of MCF7 mammary carcinoma xenografts in a non-immunocompromised rat model

“…Other chemical inducers of tumours include the administration of high doses of growth hormones, oestrogens or aminofluorene compounds that stimulate the development of mammary tumours [8]. These chemical inducers are toxic and harmful to the animal upon administration and offers low tumour development or growth rates that may take up to 3-4 months before the appearance of an external tumour growth [9].…”