Abstract
Experiments were undertaken to investigate the early effects of DMBA or progesterone, or the two in combination, on DNA synthesis in rat mammary epithelial cells, and also to determine whether there was any correlation between the level of DNA synthesis observed in the first 96 hours after administration of DMBA, either alone or combined with progesterone, and subsequent tumour development.
It was found that DMBA alone caused an insignificant reduction in DNA synthesis in the first 96 hours, whereas progesterone significantly enhanced DNA synthesis. When the carcinogen and hormone were administered together, a greater rise was seen in the level of DNA synthesis than that occurring in rats treated only with DMBA, but the increase was not significantly greater than that in untreated animals. A two-way analysis of variance revealed no interaction between DMBA and progesterone in relation to mammary epithelial cell DNA synthesis.
Mammary neoplasms occurred only in the groups of rats which had received DMBA, either alone or in combination with progesterone. No correlation could be demonstrated between the extent of DNA synthesis observed in mammary glands biopsied between 6 and 96 hours after carcinogen administration and the occurrence of tumours in the host rats 135 days later.
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.
- BROOKES P., LAWLEY P. D. EVIDENCE FOR THE BINDING OF POLYNUCLEAR AROMATIC HYDROCARBONS TO THE NUCLEIC ACIDS OF MOUSE SKIN: RELATION BETWEEN CARCINOGENIC POWER OF HYDROCARBONS AND THEIR BINDING TO DEOXYRIBONUCLEIC ACID. Nature. 1964 May 23;202:781–784. doi: 10.1038/202781a0. [DOI] [PubMed] [Google Scholar]
- Bates R. R., Wortham J. S., Counts W. B., Dingman C. W., Gelboin H. V. Inhibition by actinomycin D of DNA synthesis and skin tumorigenesis induced by 7,12-dimethylbenz(a)anthracene. Cancer Res. 1968 Jan;28(1):27–34. [PubMed] [Google Scholar]
- Clementi F., de Virgiliis G. Ultrastructure de l'adénohypophyse après ovariectomie et traitement par les oestrogènes et la progestérone. Pathol Biol. 1967 Feb;15(3):119–131. [PubMed] [Google Scholar]
- DAO T. L., GAWLAK D. Direct mammotrophic effect of a pituitary homograft in rats. Endocrinology. 1963 Jun;72:884–892. doi: 10.1210/endo-72-6-884. [DOI] [PubMed] [Google Scholar]
- Dao T. L. Studies on mechanism of carcinogenesis in the mammary gland. Prog Exp Tumor Res. 1969;11:235–261. doi: 10.1159/000391397. [DOI] [PubMed] [Google Scholar]
- FRIEDKIN M., TILSON D., ROBERTS D. Studies of deoxyribonucleic acid biosynthesis in embryonic tissues with thymidine-C14. J Biol Chem. 1956 Jun;220(2):627–637. [PubMed] [Google Scholar]
- FURTH J., CLIFTON K. H. Experimental pituitary tumors and the role of pituitary hormones in tumorigenesis of the breast and thyroid. Cancer. 1957 Jul-Aug;10(4):842–853. doi: 10.1002/1097-0142(195707/08)10:4<842::aid-cncr2820100436>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
- Fitzgerald P. J., Carol B., Lipkin L., Rosenstock L. Pancreatic acinar cell regeneration. V. Analysis of variance of the autoradiographic labeling index (thymidine-H3). Am J Pathol. 1968 Dec;53(6):953–970. [PMC free article] [PubMed] [Google Scholar]
- Flesher J. W. Distribution of radioactivity in the tissues of rats after oral administration of 7,12-dimethylbenz(A)anthracene-3H. Biochem Pharmacol. 1967 Sep 9;16(9):1821–1831. doi: 10.1016/0006-2952(67)90259-6. [DOI] [PubMed] [Google Scholar]
- Frei J. V., Harsono T. Increased susceptibility to low doses of a carcinogen of epidermal cells in stimulated DNA synthesis. Cancer Res. 1967 Aug;27(8):1482–1484. [PubMed] [Google Scholar]
- Goshman L. M., Heidelberger C. Binding of tritium-labeled polycyclic hydrocarbons to DNA of mouse skin. Cancer Res. 1967 Sep;27(9):1678–1688. [PubMed] [Google Scholar]
- HUGGINS C., MAINZER K., BRIZIARELLI G. Molecular structure of steroids and phenanthrene derivatives related to growth of transplanted mammary tumors. Recent Prog Horm Res. 1958;14:77–93. [PubMed] [Google Scholar]
- Hennings H., Boutwell R. K. The inhibition of DNA synthesis by initiators of mouse skin tumorigenesis. Cancer Res. 1969 Mar;29(3):510–514. [PubMed] [Google Scholar]
- Hennings H., Smith H. C., Colburn N. H., Boutwell R. K. Inhibition by actinomycin D of DNA and RNA synthesis and of skin carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene or beta-propiolactone. Cancer Res. 1968 Mar;28(3):543–552. [PubMed] [Google Scholar]
- Hervey E., Hervey G. R. The effects of progesterone on body weight and composition in the rat. J Endocrinol. 1967 Apr;37(4):361–381. doi: 10.1677/joe.0.0370361. [DOI] [PubMed] [Google Scholar]
- Jabara A. G. Effects of progesterone on 9,10-dimethyl-1,2-benzanthracene-induced mammary tumours in Sprague-Dawley rats. Br J Cancer. 1967 Jun;21(2):418–429. doi: 10.1038/bjc.1967.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jabara A. G., Harcourt A. G. Effects of progesterone, ovariectomy and adrenalectomy on mammary tumours induced by 7,12-dimethylbenz(a)anthracene in Sprague-Dawley rats. Pathology. 1971 Jul;3(3):209–214. [PubMed] [Google Scholar]
- Jabara A. G., Harcourt A. G. The effects of progesterone and ovariectomy on mammary tumours induced by 7,1 2-dimethylbenz(a)anthracene in Sprague-Dawley rats. Pathology. 1970 Apr;2(2):115–123. doi: 10.3109/00313027009077333. [DOI] [PubMed] [Google Scholar]
- Kim U. Pituitary function and hormonal therapy of experimental breast cancer. Cancer Res. 1965 Aug;25(7):1146–1161. [PubMed] [Google Scholar]
- Libby P. R., Dao T. L. Rat Mammary Gland RNA: Incorporation of C14-Formate and Effect of Hormones and 7,12-Dimethylbenz[alanthracene. Science. 1966 Jul 15;153(3733):303–305. doi: 10.1126/science.153.3733.303. [DOI] [PubMed] [Google Scholar]
- O'Malley B. W., Toft D. O., Sherman M. R. Progesterone-binding components of chick oviduct. II. Nuclear components. J Biol Chem. 1971 Feb 25;246(4):1117–1122. [PubMed] [Google Scholar]
- Pound A. W. The influence of preliminary irritation by acetic acid or croton oil on skin tumour production in mice after a single application of dimethyl-benzathracene, benzopyrene, or dibenzanthracene. Br J Cancer. 1968 Sep;22(3):533–544. doi: 10.1038/bjc.1968.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- REICHARD P., ESTBORN B. Utilization of desoxyribosides in the synthesis of polynucleotides. J Biol Chem. 1951 Feb;188(2):839–846. [PubMed] [Google Scholar]
- ROTHCHILD I. The corpus luteum-pituitary relationship: the association between the cause of luteotrophin secretion and the cause of follicular quiescence during lactation; the basis for a tentative theory of the corpus luteum-pituitary relationship in the rat. Endocrinology. 1960 Jul;67:9–41. doi: 10.1210/endo-67-1-9. [DOI] [PubMed] [Google Scholar]
- Sar M., Meites J. Effects of progesterone, testosterone, and cortisol on hypothalamic prolactin-inhibiting factor and pituitary prolactin content. Proc Soc Exp Biol Med. 1968 Feb;127(2):426–429. doi: 10.3181/00379727-127-32707. [DOI] [PubMed] [Google Scholar]
- Shimkin M. B., Gruenstein M., Thatcher D., Baserga R. Tritiated thymidine labeling of cells in rats following exposure to 7,12-dimethylbenz(a)anthracene. Cancer Res. 1967 Aug;27(8):1494–1495. [PubMed] [Google Scholar]
- Sinha Y. N., Schmidt G. H. Changes in pituitary prolactin and mammary nucleic acid content during pseudopregnancy in the rat. Proc Soc Exp Biol Med. 1969 Mar;130(3):867–870. doi: 10.3181/00379727-130-33675. [DOI] [PubMed] [Google Scholar]
- Sinha Y. N., Tucker H. A. Pituitary prolactin content and mammary development after chronic administration of prolactin. Proc Soc Exp Biol Med. 1968 May;128(1):84–88. doi: 10.3181/00379727-128-32948. [DOI] [PubMed] [Google Scholar]
- Spelsberg T. C., Steggles A. W., O'Malley B. W. Progesterone-binding components of chick oviduct. 3. Chromatin acceptor sites. J Biol Chem. 1971 Jul 10;246(13):4188–4197. [PubMed] [Google Scholar]
- Süss R., Maurer H. R. Reduced binding of carcinogenic hydrocarbons to DNA of mouse skin during inhibition of DNA synthesis. Nature. 1968 Feb 24;217(5130):752–753. doi: 10.1038/217752a0. [DOI] [PubMed] [Google Scholar]
- TALWALKER P. K., MEITES J., MIZUNO H. MAMMARY TUMOR INDUCTION BY ESTROGEN OR ANTERIOR PITUITARY HORMONES IN OVARIECTOMIZED RATS GIVEN 7, 12-DIMETHYL-1, 2-BENZANTHRACENE. Proc Soc Exp Biol Med. 1964 Jun;116:531–534. doi: 10.3181/00379727-116-29297. [DOI] [PubMed] [Google Scholar]
- TALWALKER P. K., MEITES J. Mammary lobulo-alveolar growth induced by anterior pituitary hormones in adrenoovariectomized and adreno-ovariectomized-hypophysectomized rats. Proc Soc Exp Biol Med. 1961 Aug-Sep;107:880–883. doi: 10.3181/00379727-107-26783. [DOI] [PubMed] [Google Scholar]
- Takizawa S., Furth J. J., Furth J. DNA synthesis in autonomous and hormone-responsive mammary tumors. Cancer Res. 1970 Jan;30(1):206–210. [PubMed] [Google Scholar]
- Tominaga T., Dao T. L., Libby P. R. Effects of 7,12-dimethylbenz (a) anthracene on RNA polymerase in isolated mammary gland cell nuclei. Proc Soc Exp Biol Med. 1971 Mar;136(3):694–697. doi: 10.3181/00379727-136-35343. [DOI] [PubMed] [Google Scholar]
- Tominaga T., Libby P. R., Dao T. L. An early effect of 7,12-dimethylbenz(a)anthracene on rat mammary gland DNA synthesis. Cancer Res. 1970 Jan;30(1):118–122. [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]

