Summary
The influence of estrogen on mammary carcinogenesis was studied in female Sprague-Dawley rats ovariectomized at the age of 36 days and given injections of 17β-estradiol (group I:0, II:1, III:10, IV: 100, V: 1000 μg/2 days) between the ages of 36 and 250 days and a single oral dose of 20 mg of 7,12-dimethylbenz(a) anthracene (DMBA) at the age of 50 days. No palpable mammary carcinomas were detected up to the age of 135 days. At the age of 135 days, each group was divided into two subgroups (a and b). Rats of the second subgroup (Ib, IIb, IIIb, IVb and Vb) were given additional injections of progesterone (P; 4 mg/2 days) between the ages of 135 and 250 days. At the age of 250 days, the incidence of mammary carcinoma was significantly higher in rats from group IIIb than in groups Ib and IIIa, and that in group IVa was also higher than in group Ia. The incidence in group IVb was significantly lower than in group IVa. The carcinomas in group IIIb were palpable papillo-tubular adenocarcinomas and those in group IVa were secretory micro-adenocarcinomas. These results indicate that the induction of mammary carcinomas byDMBA is totally inhibited by ovariectomy and/or high doses of estrogen, but that mammary carcinomas are initiated byDMBA under hormonal conditions in which suitable levels of estrogen are present. They also suggest that the growth ofDMBA-induced mammary carcinomas in the rats from group III were accelerated by additional injections of P and that those in rats from group IV were inhibited by additional P. The mammary glands of 50-day-old rats in groups III and IV contained more terminal ducts and terminal ends buds or lobules with BrdU-positive cells than those of rats in other groups.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Banerjee MR, Rogers FM (1971) Stimulation of the synthesis of macromolecules by ovarian hormones during early development of the mouse mammary gland. J Endocrinol 49:39–49
Bodwin JS, Hirayama PH, Rego JA, Cho-Chung YS (1981) Regression of hormone-dependent mammary tumors in Sprague-Dawley rats as a result of tamoxifen or pharmacologic doses of 17-estradiol: cyclic adenosine 3,5-monophosphate-mediated events. J Natl Cancer Inst 66:321–326
Hirayama T, Wynder EL (1962) A study of the epidemiology of cancer of the breast. II. The influence of hysterectomy. Cancer 15:28–38
Huggins C, Grand LC, Brillantes FP (1961) Mammary cancer induced by a single feeding of polynuclear hydrocarbons, and its suppression. Nature 189:204–207
Huggins C, Yang NC (1962) Induction and extinction of mammary cancer. A striking effect of hydrocarbons permits analysis of mechanisms of causes and cure of breast cancer. Science 137:257–262
Kiang DT, Kennedy BJ (1971) Combination of cyclophosphamide and estrogen therapy in DMBA-induced rat mammary cancer. Cancer 28:1202–1210
Mainland D, Murray IM (1952) Tables for use in fourfold contingency test. Science 116:519–524
Morstyn G, Hsu SM, Kinsella T, Gratzner H, Russo A, Mitchell JB et al. (1983) Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. J Clin Investigation 72:1844–1850
Murad T, von Haam E (1972) Studies of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene administration. Cancer Res 32:1404–1415
Nagasawa H, Yanai R (1974) Frequency of mammary cell division in relation to age: Its significance in the induction of mammary tumors by carcinogen in rats. J Natl Cancer Inst 52:609–610
Nagasawa H, Yanai R, Taniguchi H (1976) Importance of mammary gland DNA synthesis on carcinogen-induced mammary tumorigenesis in rats. Cancer Res 36:2223–2226
Russo IH, Russo J (1978) Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12 dimethylbenz[a]anthracene. J Natl Cancer Inst 61:1439–1449
Russo J, Russo IH (1978) DNA labeling index and structure of the rat mammary gland as determinants of its susceptibility to carcinogenesis. J Natl Cancer Inst 61:1451–1459
Russo J, Russo IH (1980a) Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence. Am J Pathol 100:497–512
Russo J, Russo IH (1980b) Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland carcinogenesis. Cancer Res 40:2677–2687
Russo J, Saby J, Isenberg WM, Russo IH (1977) Pathogenesis of mammary carcinomas induced in rats by 7,12-dimethylbenz[a]anthracene. J Natl Cancer Inst 59:435–445
Russo J, Wilgus G, Russo IH (1979) Susceptibility of the mammary gland to carcinogenesis. I. Differentiation of the mammary gland as determinant of tumor incidence and type of lesion. Am J Pathol 96:721–736
Russo J, Tait L, Russo IH (1983) Susceptibility of the mammary gland to carcinogenesis. III. The cell of origin of rat mammary carcinoma. Am J Pathol 113:50–66
Talwalker PK, Meites J, Mizuno H (1964) Mammary tumor induction by estrogen or anterior pituitary hormones in ovariectomized rats given, 7,12-dimethyl-l,2-benzanthracene. PSEBM 116:531–534
Tokunaga M, Land CE, Yamamoto T, Asano M, Tokuoka S, Ezaki H, Nishimori I (1987) Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950–1980. Radiat Res 112:243–272
Yoshida H, Fukunishi R, Kato Y, Matsumoto K (1980a) Progesterone-stimulated growth of mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene in neonatally androgenized rats. J Natl Cancer Inst 65:823–828
Yoshida H, Kadota A, Fukunishi R, Matsumoto K (1980b) Induction of mammary dysplasia and mammary carcinoma in neonatally androgenized female rats by 7,12-dimethylbenz[a] anthracene. J Natl Cancer Inst 64:1105–1112
Yoshida H, Kadota A, Fukunishi R (1980c) Pathology of early lesions of mammary carcinoma and mammary dysplasia induced by 7,12-dimethylbenz[a]anthracene in the neonatally androgenized Sprague-Dawley female rats. Virchows Arch [B] 34:33–41
Yoshida H, Yoshida A, Noguchi S, Matsumoto K (1987) Establishment of pharmacological doses of estrogen-dependent mammary tumors with estrogen and progesterone receptors. In Vivo 1:157–162
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ohi, Y., Yoshida, H. Influence of estrogen and progesterone on the induction of mammary carcinomas by 7,12-dimethylbenz(a)anthracene in ovariectomized rats. Virchows Archiv B Cell Pathol 62, 365–370 (1992). https://doi.org/10.1007/BF02899705
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02899705