An Autoradiographic Study of the Early Effects of 7,12-Dimethylbenz(a)anthracene and Progesterone on DNA Synthesis in Rat Mammary Epithelial Cells and Subsequent Tumour Development

Summary.-The effects of hormone and drug treatments on plasma prolactin (PRL) levels and mammary tumour growth were investigated in rats bearing continuously growing DMBA-induced mammary tumours that responded to bilateral adrenoovariectomy (Ax+ Ox). Oestrogen (E2) administration increased both plasma PRL and tumour growth, but was unable to sustain tumour growth when the PRL level was reduced by concurrent injection of ergocornine (Eg). Perphenazine (P,) produced a dose-related increase in plasma PRL, but stimulation of tumour growth in the absence of E2 required a minimal level of plasma PRL induced by Pz (0-15 mg/100 g body wt/day or more). Progesterone (P) (3 mg/day) alone, although without effect on PRL levels, maintained static tumour growth (i.e. it had a slight stimulatory effect) irrespective of the duration of treatment. The increase in plasma PRL levels above the basal values in the Ax + Ox controls following injections of combined P + P, (0 1 mg/100 g/day) was sufficient to sustain static tumour growth, but not to reactivate growth. Enhancement of both plasma PRL and tumour growth did not occur until P and higher doses of Pz (0.3 mg/100 g/day) were injected jointly; this treatment, however, while unable to stimulate continuous tumour growth, was able to maintain static growth when plasma PRL was reduced by concurrent injections of P+Pz+Eg. From these findings it is postulated that the mechanism of action whereby P maintains static tumour growth is different from that of PRL and independent of circulating PRL levels.

Section: Discussionmentioning

confidence: 78%

Hormone and drug effects on growth of DMBA mammary tumours and plasma prolactin levels in adreno-ovariectomized rats

Minasian-Batmanian¹,

Jabara²

1981

“…Incorporation of label into Table I). The variation between samples, and the failure to observe a discrete peak of radioactive incorporation, may have been caused by random distribution of the rats with respect to the stage in the oestrous cycle (Jabara, Toyne and Fisher, 1972). Among those rats surviving at least 10 weeks after treatment, 5 rats were found to have a total of 6 salivary gland tumours (Table 11).…”

Section: Resultsmentioning

confidence: 99%

The effect of isoprenaline on induction of tumours by methyl nitrosourea in the salivary and mammary glands of female wistar rats

Parkin¹,

Neale²

1976

“…It was observed previously that the greatest depression in carcinogenesis occurred when progesterone treatment was stopped 7 days before feeding DMBA (Jabara et al, 1973) and this was the hormone regime adopted in the present study. However, it was also previously observed that it took about 10 days from cessation of progesterone injections before the rats began to cycle normally, indicating that time is required for the subcutaneous hormone depot to be totally absorbed, metabolized and excreted (Jabara et al, 1972) and hence progesterone must still have been present when the carcinogen was administered 7 days after hormone injections ceased. Therefore, Dao's (1971) (Bock & Dao, 1961;Gammal et al, 1965;Flesher, 1967;Dao et al, 1968 On the other hand, possibly a more likely explanation for the abolition of the inhibitory effect of progesterone pretreatment in the present experiment may be that the hormone acts at a site other than the breast tissue itself, perhaps on the liver.…”

Section: D)iscussionmentioning

confidence: 98%

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

Jabara¹,

Marks²,

Summers³

et al. 1979

Summary.-The effects and site(s) of action of progesterone on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen was applied directly to the inguinal mammary gland, were investigated.No reduction in tumour yield was apparent when progesterone was administered s.c. for 18 days before dusting DMBA. This finding contrasts with a previously reported inhibitory effect on carcinogenesis when hormone treatment was followed by intragastric administration of DMBA.When progesterone injections were begun either 2 days before or 2 days after direct application of DMBA, and were continued until the end of the experiment (135 or 195 days) an enhancement in carcinogenesis was observed similar to that previously demonstrated after gastric intubation of DMBA.These findings, together with previously reported observations, suggest that progesterone may exert its inhibitory effect on carcinogenesis by acting at a site outside the breast, perhaps on the liver. However, it is likely that the hormone acts directly on the mammary tissue to exert its enhancing effect on tumorigenesis.