Abstract
A single intraperitoneal inoculation of 180 mg/kg N-ethyl-N-nitrosourea (ENU) into 30-day-old outbred Sprague-Dawley (CD) rats resulted in an 90% incidence of mammary tumors (MTs) after an average latent period of 93 days, with an 85% rate of malignancy. The incidence, induction period, number of tumors per rats, and the rate of malignancy were reduced in rats ovariectomized prior to or shortly after (5 days) ENU exposure. Over 70% of the ENU-induced MTs regressed following ovarioectomy. The malignant MTs developed from nodules located in the terminal end buds (TEB), which are believed to contain the most susceptible cell population for chemical carcinogens. The serum calcium was elevated above control values in 92% of intact rats evaluated with MTs in the absence of bone metastases. No correlation was demonstrated between the volume of MTs or total number of MTs and the serum calcium level. The ENU-induced MT is a reproducible animal model that can be used in the investigation of the early changes in mammary cells (especially TEB) and the interrelationships between the carcinogen and ovarian hormones associated with neoplastic transformation.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Besarab A., Caro J. F. Mechanisms of hypercalcemia in malignancy. Cancer. 1978 Jun;41(6):2276–2285. doi: 10.1002/1097-0142(197806)41:6<2276::aid-cncr2820410628>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Beuving L. J., Faulkin L. J., Jr, DeOme K. B., Bergs V. V. Hyperplastic lesions in the mammary glands of Sprague-Dawley rats after 7,12-dimethyl-benz[a]anthracene treatment. J Natl Cancer Inst. 1967 Sep;39(3):423–429. [PubMed] [Google Scholar]
- Bucclarelli E. Mammary tumor induction in male and female Sprague-Dawley rats by adriamycin and daunomycin. J Natl Cancer Inst. 1981 Jan;66(1):81–84. [PubMed] [Google Scholar]
- DAO T. L. CARCINOGENESIS OF MAMMARY GLAND IN RAT. Prog Exp Tumor Res. 1964;5:157–216. doi: 10.1159/000385999. [DOI] [PubMed] [Google Scholar]
- Druckrey H., Landschütz C., Ivankovic S. Transplacentare Erzeugung maligner Tumoren des Nervensystems. II. Athyl-nitrosoharnstoff an 10 genetisch definierten Rattenstämmen. Z Krebsforsch. 1970 Mar 10;73(4):371–386. [PubMed] [Google Scholar]
- Durbin P. W., Williams M. H., Jeung N., Arnold J. S. Development of spontaneous mammary tumors over the life-span of the female Charles River (Sprague-Dawley) rat: the influence of ovariectomy, thyroidectomy, and adrenalectomy-ovariectomy. Cancer Res. 1966 Mar;26(3):400–411. [PubMed] [Google Scholar]
- Friedman M. A., Hoffman P. G., Jr, Dandolos E. M., Lagios M. D., Johnston W. H., Siiteri P. K. Estrogen receptors in male breast cancer: clinical and pathologic correlations. Cancer. 1981 Jan 1;47(1):134–137. doi: 10.1002/1097-0142(19810101)47:1<134::aid-cncr2820470122>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
- Gullino P. M., Pettigrew H. M., Grantham F. H. N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst. 1975 Feb;54(2):401–414. [PubMed] [Google Scholar]
- KENNEDY B. J., FORTUNY I. E. THERAPEUTIC CASTRATION IN THE TREATMENT OF ADVANCED BREAST CANCER. Cancer. 1964 Sep;17:1197–1202. doi: 10.1002/1097-0142(196409)17:9<1197::aid-cncr2820170916>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- Koestner A., Swenberg J. A., Wechsler W. Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Am J Pathol. 1971 Apr;63(1):37–56. [PMC free article] [PubMed] [Google Scholar]
- Mandybur T. I., Ormsby I., Buncher C. R. Enhanced development of mammary tumors in rats following transplacental and neonatal exposure to ethylnitrosourea. Cancer Res. 1978 Oct;38(10):3182–3185. [PubMed] [Google Scholar]
- Marcum R. G., Wellings S. R. Subgross pathology of the human breast: method and initial observations. J Natl Cancer Inst. 1969 Jan;42(1):115–121. [PubMed] [Google Scholar]
- Muggia F. M., Heinemann H. O. Hypercalcemia associated with neoplastic disease. Ann Intern Med. 1970 Aug;73(2):281–290. doi: 10.7326/0003-4819-73-2-281. [DOI] [PubMed] [Google Scholar]
- Mulder J. B. Anesthesia in the mouse using a combination of ketamine and promazine. Lab Anim Sci. 1978 Feb;28(1):70–71. [PubMed] [Google Scholar]
- Murad T. M., Von Haam E. Studies of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene administration. Cancer Res. 1972 Jul;32(7):1404–1415. [PubMed] [Google Scholar]
- Nagasawa H., Yanai R. Effects of prolactin or growth hormone on growth of carcinogen-induced mammary tumors of adreno-ovariectomized rats. Int J Cancer. 1970 Nov 15;6(3):488–495. doi: 10.1002/ijc.2910060320. [DOI] [PubMed] [Google Scholar]
- Russo I. H., Russo J. Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz[a]anthracene. J Natl Cancer Inst. 1978 Dec;61(6):1439–1449. [PubMed] [Google Scholar]
- Russo J., Russo I. H. Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence. Am J Pathol. 1980 Aug;100(2):497–512. [PMC free article] [PubMed] [Google Scholar]
- Russo J., Wilgus G., Russo I. H. 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. 1979 Sep;96(3):721–736. [PMC free article] [PubMed] [Google Scholar]
- SCOTT K. G., SCHELINE R. R., STONE R. S. Mast cells and sarcoma growth in the rat. Cancer Res. 1958 Sep;18(8 Pt 1):927–931. [PubMed] [Google Scholar]
- WADA Y., TAMURA J., TOMITA Y., YAMADA M. [Relation between mast cells and tumor cells in ascites hepatoma and Takeda sarcoma]. Gan. 1955 Sep;46(2-3):397–398. [PubMed] [Google Scholar]
- Wellings S. R., Jensen H. M. On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst. 1973 May;50(5):1111–1118. doi: 10.1093/jnci/50.5.1111. [DOI] [PubMed] [Google Scholar]
- Williams J. C., Gusterson B., Humphreys J., Monaghan P., Coombes R. C., Rudland P., Neville A. M. N-methyl-N-nitrosourea-induced rat mammary tumors. Hormone responsiveness but lack of spontaneous metastasis. J Natl Cancer Inst. 1981 Jan;66(1):147–155. [PubMed] [Google Scholar]





