Abstract
In the rat, pregnancy and lactation prior to carcinogen administration protect the mammary gland from developing carcinomas and benign lesions. In this study, the influence of pregnancy interruption versus full pregnancy and pregnancy plus lactation on the incidence of carcinomas and benign lesions was studied in the mammary glands of rats treated with 7,12-dimethylbenz(a)anthracene (DMBA). Fifty-nine Sprague-Dawley rats were separated into 5 groups: I) rats that had had one pregnancy and one lactation; II) rats that had had one pregnancy without lactation; III) rats that had had pregnancy interrupted at the 12th day of gestation; IV) age-matched virgin rats as a control Group I; and V) age-matched virgin rats as a control for groups II and III. The 5 groups received a single intragastric dose of DMBA (10 mg/100 g body weight), with the exception of 2 animals per group, which were killed 1 hour after an intraperitoneal injection of 2.5 mu Ci 3H-thymidine/g body weight. The number of labeled nuclei per 100 cells (DNA labeling index, LI) was counted in terminal end buds (TEBs), terminal ducts (TDs), and alveolar buds (ABs) of the glands. The number of structures and the DNA-LI were correlated with the incidence of tumors at 22 weeks after DMBA. Pregnancy, with or without lactation, resulted in elimination of TEBs and reduction in the DNA-LI of TDs and ABs. These groups did not develop carcinomas. After the interruption of pregnancy the mammary gland contained numerous TEBs, with a high DNA-LI; 77% of these animals developed carcinomas, and all of them developed benign lesions. Therefore, while pregnancy and lactation protected the mammary gland from developing carcinomas and benign lesions by induction of full differentiation, pregnancy interruption did not elicit sufficient differentiation in the gland to be protective, and these animals were at the same risk as virgin animals treated with the carcinogen.
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- Cole P., MacMahon B. Oestrogen fractions during early reproductive life in the aetiology of breast cancer. Lancet. 1969 Mar 22;1(7595):604–606. doi: 10.1016/s0140-6736(69)91537-2. [DOI] [PubMed] [Google Scholar]
- DAO T. L., BOCK F. G., GREINER M. J. Mammary carcinogenesis by 3-methylcholanthrene. II. Inhibitory effect of pregnancy and lactation on tumor induction. J Natl Cancer Inst. 1960 Nov;25:991–1003. [PubMed] [Google Scholar]
- DAO T. L., SUNDERLAND H. Mammary carcinogenesis by 3-methylcholanthrene. I. Hormonal aspects in tumor induction and growth. J Natl Cancer Inst. 1959 Sep;23:567–585. [PubMed] [Google Scholar]
- De Waard F., Cornelis J. P., Aoki K., Yoshida M. Breast cancer incidence according to weight and height in two cities of the Netherlands and in Aichi prefecture, Japan. Cancer. 1977 Sep;40(3):1269–1275. doi: 10.1002/1097-0142(197709)40:3<1269::aid-cncr2820400341>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
- Huggins C., Grand L. C., Brillantes F. P. CRITICAL SIGNIFICANCE OF BREAST STRUCTURE IN THE INDUCTION OF MAMMARY CANCER IN THE RAT. Proc Natl Acad Sci U S A. 1959 Aug;45(8):1294–1300. doi: 10.1073/pnas.45.8.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hwang P., Guyda H., Friesen H. A radioimmunoassay for human prolactin. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1902–1906. doi: 10.1073/pnas.68.8.1902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juret P., Couette J. E., Brune D., Vernhes J. C. L'âge à la première naissance: une variable à la signification simple, double ou triple en cancérologie mammaire. Bull Cancer. 1975 Apr-Jun;62(2):165–174. [PubMed] [Google Scholar]
- Juret P., Couette J. E., Mandard A. M., Carré A., Delozier T., Brune D., Vernhes J. C. Age at menarche as a prognostic factor in human breast cancer. Eur J Cancer. 1976 Sep;12(9):701–704. doi: 10.1016/0014-2964(76)90019-0. [DOI] [PubMed] [Google Scholar]
- Kledzik G. S., Bradley C. J., Meites J. Reduction of carcinogen-induced mammary cancer incidence in rats by early treatment with hormones or drugs. Cancer Res. 1974 Nov;34(11):2953–2956. [PubMed] [Google Scholar]
- Lin T. M., Chen K. P., MacMahon B. Epidemiologic characteristics of cancer of the breast in Taiwan. Cancer. 1971 Jun;27(6):1497–1504. doi: 10.1002/1097-0142(197106)27:6<1497::aid-cncr2820270634>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- MACMAHON B., FEINLEIB M. Breast cancer in relation to nursing and menopausal history. J Natl Cancer Inst. 1960 Mar;24:733–753. doi: 10.1093/jnci/24.3.733. [DOI] [PubMed] [Google Scholar]
- MARCHANT J. Influence of pregnancy and lactation on the incidence of mammary carcinoma induced with methylcholanthrene in female mice of the "IF" strain. J Pathol Bacteriol. 1955 Oct;70(2):415–418. doi: 10.1002/path.1700700218. [DOI] [PubMed] [Google Scholar]
- MARCHANT J. Local inhibition by lactation of chemically induced breast tumours in mice of the IF strain. Nature. 1959 Feb 28;183(4661):629–629. doi: 10.1038/183629a0. [DOI] [PubMed] [Google Scholar]
- MARCHANT J. The inhibitory effect of continued lactation on the incidence of chemically-induced breast tumours in mice of the IF strain. Br J Cancer. 1958 Mar;12(1):55–61. doi: 10.1038/bjc.1958.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MAZZOLENI G. F. [Frequency relationships between mammary carcinoma and pregnancy]. Riv Anat Patol Oncol. 1960 Feb;17:243–260. [PubMed] [Google Scholar]
- MCCORMICK G. M., MOON R. C. EFFECT OF PREGNANCY AND LACTATION ON GROWTH OF MAMMARY TUMOURS INDUCED BY 7,12-DIMETHLBENZ(A) ANTHRACENE (DMBA). Br J Cancer. 1965 Mar;19:160–166. doi: 10.1038/bjc.1965.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacMahon B., Cole P., Brown J. Etiology of human breast cancer: a review. J Natl Cancer Inst. 1973 Jan;50(1):21–42. doi: 10.1093/jnci/50.1.21. [DOI] [PubMed] [Google Scholar]
- McCormick G. M., Moon R. C. Effect of increasing doses of estrogen and progesterone on mammary carcinogenesis in the rat. Eur J Cancer. 1973 Jul;9(7):483–486. doi: 10.1016/0014-2964(73)90131-x. [DOI] [PubMed] [Google Scholar]
- McGregor H., Land C. E., Choi K., Tokuoka S., Liu P. I., Wakabayashi T., Beebe G. W. Breast cancer incidence among atomic bomb survivors, Hiroshima and Nagasaki, 1950-69. J Natl Cancer Inst. 1977 Sep;59(3):799–811. doi: 10.1093/jnci/59.3.799. [DOI] [PubMed] [Google Scholar]
- Miller A. B. Role of nutrition in the etiology of breast cancer. Cancer. 1977 Jun;39(6 Suppl):2704–2708. doi: 10.1002/1097-0142(197706)39:6<2704::aid-cncr2820390657>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
- Moon R. C. Relationship between previous reproductive history and chemically induced mammary cancer in rats. Int J Cancer. 1969 May 15;4(3):312–317. doi: 10.1002/ijc.2910040308. [DOI] [PubMed] [Google Scholar]
- Nagasawa H., Yanai R. Effect of human placental lactogen on growth of carcinogen-induced mammary tumors in rats. Int J Cancer. 1973 Jan 15;11(1):131–137. doi: 10.1002/ijc.2910110115. [DOI] [PubMed] [Google Scholar]
- Petrakis N. L. Genetic factors in the etiology of breast cancer. Cancer. 1977 Jun;39(6 Suppl):2709–2715. doi: 10.1002/1097-0142(197706)39:6<2709::aid-cncr2820390658>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- ROY E. J., MACKAY R. The concentration of oestrogens in blood during pregnancy. J Obstet Gynaecol Br Emp. 1962 Feb;69:13–17. doi: 10.1111/j.1471-0528.1962.tb00002.x. [DOI] [PubMed] [Google Scholar]
- Ravnihar B., MacMahon B., Lindtner J. Epidemiologic features of breast cancer in Slovenia, 1965-1967. Eur J Cancer. 1971 Aug;7(4):295–306. doi: 10.1016/0014-2964(71)90072-7. [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. DNA labeling index and structure of the rat mammary gland as determinants of its susceptibility to carcinogenesis. J Natl Cancer Inst. 1978 Dec;61(6):1451–1459. [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]
- Shapiro S., Strax P., Venet L., Fink R. The search for risk factors in breast cancer. Am J Public Health Nations Health. 1968 May;58(5):820–835. doi: 10.2105/ajph.58.5.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valaoras V. G., MacMahon B., Trichopoulos D., Polychronopoulou A. Lactation and reproductive histories of breast cancer patients in greater Athens, 1965-67. Int J Cancer. 1969 May 15;4(3):350–363. doi: 10.1002/ijc.2910040312. [DOI] [PubMed] [Google Scholar]
- WYNDER E. L., BROSS I. J., HIRAYAMA T. A study of the epidemiology of cancer of the breast. Cancer. 1960 May-Jun;13:559–601. doi: 10.1002/1097-0142(196005/06)13:3<559::aid-cncr2820130322>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
- Welsch C. W., Clemens J. A., Meites J. Effects of multiple pituitary homografts or progesterone on 7,12-dimethylbenz[a]anthracene-induced mammary tumors in rats. J Natl Cancer Inst. 1968 Aug;41(2):465–471. [PubMed] [Google Scholar]
- Welsch C. W., Meites J. Effects of a norethynodrel-mestranol combination (enovid) on development and growth of carcinogen-induced mammary tumors in female rats. Cancer. 1969 Mar;23(3):601–607. doi: 10.1002/1097-0142(196903)23:3<601::aid-cncr2820230312>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- Yoshimi T., Strott C. A., Marshall J. R., Lipsett M. B. Corpus luteum function in early pregnancy. J Clin Endocrinol Metab. 1969 Feb;29(2):225–230. doi: 10.1210/jcem-29-2-225. [DOI] [PubMed] [Google Scholar]
- Yuasa S., MacMahon B. Lactation and reproductive histories of breast cancer patients in Tokyo, Japan. Bull World Health Organ. 1970;42(2):195–204. [PMC free article] [PubMed] [Google Scholar]










