Effects of Time and Duration of Progesterone Administration on Mammary Tumours Induced by 7,12-Dimethylbenz(a)Anthracene in Sprague-Dawley Rats

Abstract

Summary.-A reduction in tumour yield was apparent when progesterone administration was begun 25 days before feeding 7,12-dimethylbenz(a)anthracene (DMBA).This effect was most obvious when the duration of hormone administration was brief. Continuation of progesterone for some time after feeding DMBA caused a progressive diminution of the inhibitory effect, and 135 days of continuous hormone treatment entirely abolished the effects of 25 days pretreatment with the hormone.In contrast, when progesterone injections were begun 2 days after feeding DMBA, there was a trend towards enhancement of tumour yield. Continuous hormone administration appeared more effective than shorter treatment regimens.PREVIOU-S investigations have shown that exogenous progesterone, while not carcinogenic per se, significantly enhances 7,1 2-dimethylbenz(a)anthracene (DMBA) mammary tumorigenesis in entire rats. This effect was shown when continuous hormone injections were begun 2 days before or 15 days after carcinogen administration or after the first tumour had appeared (Jabara, 1967; Jabara and Harcourt, 1970), or when daily injections of progesterone were given for only 30 days, beginning 15 days after feeding DMBA (Huggins, Moon and Morii, 1962). In contrast, Welsch, Clemens and Meites (1968) reported that prolonged (25 days) daily treatment with progesterone before administering DMBA significantly inhibited mammary tumorigenesis, even although hormone injections were continued for 1 5 days after carcinogen administration.The present experiments were designed to determine the effect of variations in the time at which hormone administration was begun, and in the duration of hormone treatment, on the enhancing effect of 5 progesterone on DMBA mammary tumorigenesis. MATERIALS AND METHODSOne hundred and forty-eight non-inbred Sprague-Dawley virgin female rats were divided randomly into 8 progesterone-treated groups of 16 rats each and one control group of 20 animals ( Table I). They were housed 5 rats/cage and fed commercial pellets and water ad libitum. At 50 days of age each rat in all 9 groups was fed by gastric intubation with a single dose of 30 mg of DMBA (Eastman Organic Chemicals, U.S.A.) dissolved in 2 ml of corn oil. In addition, each animal in Groups 2-9 received subcutaneous injections of 3 mg of progesterone (Sigma Chemical Co., U.S.A.) dissolved in 0-1 ml of corn oil/day 3 times a week. In Groups 2-5, progesterone injections were begun 25 days before DMBA administration (i.e. on their 25th day of age) (DMBA + P -25) and were continued for 18, 36, 54 and 160 days for Groups 2-5 respectively. In Groups 6-9, hormone injections were begun 2 days after feeding DMBA

Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae

“…The last finding was especially obvious in the longer-term group (7), the benign tumours appearing either alone or co-existing with a mammary carcinoma. A similar hastening effect on tumours had been found when progesterone was administered after gastric intubation of the carcinogen (Jabara, 1967;Jabara et al, 1973).…”

“…In contrast, when daily progesterone injections were begun either 2 days before or 2 days after feeding DMBA and were continued until the end of the experiment (135 or 195 days), a significant enhancement in mammary carcinogenesis was obtained (Jabara & Harcourt, 1970;Jabara et al, 1973).…”

“…PREVIOUS INVESTIGATIONS have shown that exogenous progesterone (not carcinogenic per se) significantly reduced the tumour yield in Sprague-Dawley female rats when the hormone was administered for 18 days beginning 25 days before feeding a single dose of 7,12-dimethylbenz(a) anthracene (Jabara et al, 1973). In contrast, when daily progesterone injections were begun either 2 days before or 2 days after feeding DMBA and were continued until the end of the experiment (135 or 195 days), a significant enhancement in mammary carcinogenesis was obtained (Jabara & Harcourt, 1970;Jabara et al, 1973).…”

The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer

“…However, there was already evidence that challenged this dogma. Pg or MPA administered in certain schedules of carcinogenesis protocols increased mammary tumor incidence in rats (Young 1961, Jabara 1967, Jabara et al 1973, in mice carrying endogenous MMTV (van Nie 1964, Sluyser & Van Nie 1974, and in cats and dogs (Hernandez et al 1975, Concannon et al 1981. In addition, Pg (Watson et al 1979) and MPA (Formelli et al 1985) stimulated the growth of the MXT transplantable mouse tumors.…”

Circadian variations in 32P uptake of a DMBA-induced mammary tumour and Walker carcinosarcoma in rats

“…A hormone-dependent mammary tumour induced by administration of 20 mg 7,12-dimethylbenz(a)anthracene per os (Daniel and Prichard, 1967;Jabara, 1967;Jabara, Toyne and Harcourt, 1973;Teller et al, 1969). They were mainly classified as adenocarcinomata.…”