The histogenesis of mammary tumours induced in the rat by chemical carcinogens

Abstract

WHEREAS many studies deal with the histogenesis of mammary tumours in mice and in man (Bonser, Dossett and Jull, 1961), the literature contains relatively little information on the development of breast tumours in the rat (Noble and Cutts, 1959). Geschickter (1943) described the early neoplastic lesions induced by chronic oestrogenic stimulation but later studies employing chemical carcinogens for the induction of breast tumours were primarily concerned with the histology of advanced neoplasms (Ross, Scarf and Skoryna, 1953;Young et al.. 1963). It was the purpose of the experiments presented in this paper to fill the gap.The biological behaviour and endocrine response of rat mammary cancers indicate a greater similarity to human disease than those of the mouse (Huggins, 1960). In the human, mammary carcinoma arises most frequently in the ducts and ductules (Cheatle and Cutler, 1931; Muir, 1941), whereas in the mouse most carcinomas are of acinar origin (Bonser, 1945(Bonser, , 1954. The question therefore arose whether or not some interconnection existed between site of origin and biological behaviour-i.e. did mammary carcinoma in the rat arise preferentially in ductal structures?For the induction of breast tumours the three compounds, 2-acetylaminofluorene (2-AAF), 20-methyl-cholanthrene (MC) and 7,12-dimethylbenz(a)anthracene (DMBA) were chosen. The three locally available strains of rats were tested for their response to these carcinogens in preliminary trials. Wistar rats were the most susceptible and were subsequently used in the majority of experiments. MATERIALS AND METHODSOne hundred and twenty-six female rats were used in this study. The aniimals were divided into 5 experimental groups and treated as follows:Group A.-56 Wistar rats received 2-AAF in a wet diet for 13 weeks (4 mg. 2-AAF per rat per day for 9 weeks then 2 mg. per day per rat for 4 weeks). Seven of these animals were subjected to left-sided nipplectomies (6 nipples) under ether anaesthesia with prior removal of the hair from the pelt by the application of barium sulphide paste.Group B.-16 Wistars, 8 piebalds and 8 black rats were each given a single gastric instillation of DMBA (Huggins, Grand and Brillantes, 1961) by means of a 17-gauge needle tipped by a smooth soft metal perforated bulb and connected to a syringe. Each rat received 1 mg. of DMBA per 7 g. of body weight. The DMBA dose of 15-17 mg. was dissolved in 1 ml. of warm almond oil.

Mammary-tumour incidence in Sprague-Dawley rats treated with 7,12-dimethylbenz(a)anthracene: Effect of pregnancy and lack of effect of unilateral lactation

“…This was true in both unmated females, confirming the report of Middleton (1965), and in mated rats with unilateral lactation. Previous reports of decreasing tumour incidence with increasing age at DMBA administration (Huggins et al, 1961;Dao,1969) and of the protective effects of early but not delayed pregnancy (Dao et al, 1960) were, however, confirmed.…”

Induction of mammary fibroadenomas in rats by adenovirus type 9

“…'i 100. (Faulkin et al, 1967;Middleton, 1965). Such turnours have not previously been reported in rats after inoculation of oncogenic viruses.…”

Histopathogenesis of 7,12-diemthylbenz(a)anthracene-induced rat mammary tumors.

“…It has been reported that approximately 80% of the tumors arising are ovarian hormone-dependent (14,15). Rat mammary carcinomas are claimed to arise in small mammary ducts (16)(17)(18) or from hyperplastic alveolar nodules (19,20). The work presented here was undertaken to describe the histopathogenesis of rat DMBA-induced ovary-dependent tumors and ovary-independent mammary tumors in order to identify their site(s) of origin and to reexamine the preneoplastic nature of DMBAinduced mammary gland dysplasias.…”