Preventive effects of antioestrogen on mammary and pituitary tumorigenesis in rats

Abstract

Summary Six groups of inbred male Wistar/Furth (WF) rats were castrated at 40 days of age and group I received no further treatment. Groups 3 and 5 received 5.0mg diethylstilboestrol (DES) pellets. Groups 4 and 6 were given both DES and 5.0mg anti-oestrogen (antiE) clomiphene citrate pellets. At 50-55 days of age groups 2, 5, and 6 were exposed daily to drinking water containing 5.0mg N-nitrosobutylurea (NBU), for Anti-oestrogen (antiE) has been known to mimic oestrogenic action and to prevent oestrogen from expressing its full effects on target tissues (Katzenellenbogen et al., 1979;Kurl & Borthwick, 1980). AntiE has been used in the treatment of patients with breast cancer (Heuson et al., 1975). It has also been shown recently to suppress both hormone release and the growth of prolactinsecreting pituitary tumours in rats (DeQuijida et al., 1980) and in man (Lamberts et al., 1982). We have reported in a recent study that the dopamine agonist, 2-bromoergocriptine (CB-154), induced a marked and concomitant suppression of mammary and pituitary tumorigenesis in castrated male rats given diethylstilboestrol (DES) and N-nitrosobutylurea (NBU) (Sumi et al., 1983). Thus, the present study was performed to investigate the influence of antiE on tumorigenesis in the mammary and pituitary glands and to clarify whether the anti-MT effect of antiE is mainly due to impairment of oestrogen-stimulated prolactin secretion or direct blocking of the action of oestrogen on the mammary gland.We have also compared the inhibitory effects of antiE and CB-154 on the development of MT.

Effect of drugs on pituitary ultrastructure

“…3) and their hormone secretion can be reduced by bromocriptine (Niwa et al, 1987; 1986a). The development of those experimental adenomas but also of spontaneous adenomas can be prevented by dopomine agonists (Dall'Ara et al, 1988;El Etreby et al, 1983) and by the antiestrogens clomiphene (Sumi et al, 1984) and tamoxifen (De Quijada et al, 1980).…”

Estrogen-induced endogenous DNA adduction: possible mechanism of hormonal cancer.

“…However, a number of important carcinogens (8) exist that do not fit this description and therefore have been classified as nongenotoxic carcinogens (9). While their mechanism of action has not as yet been defined, some of them [such as estrogens (10)(11)(12)(13) and the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (14,15)] have been shown to promote transformation-i.e., they facilitate the expression of neoplastic properties of previously initiated susceptible cells. Estrogens were found to be negative in short-term assays for the induction of gene mutations, irrespective of whether this was measured in prokaryotic (16,17) or eukaryotic (18,39) cells.…”