Abstract
The effect of the placental hormone chorionic gonadotropin (hCG) on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumours was studied in young virgin Sprague-Dawley rats. This hormone when administered at a dose of 100 IU day-1 does not induce toxic effects, measured as alterations in body weight or weight of endocrine organs, and has a reversible effect on oestrous cycle. The lack of toxicity and the fact that hCG treatment terminated prior to administration of the chemical carcinogen DMBA protects the mammary gland from malignant transformation, led us to test the effect of hCG treatment on DMBA-initiated mammary tumours. Fifty day-old virgin Sprague-Dawley rats received intragastrically 8 mg DMBA per 100 g body weight and were divided into two groups: group I animals were treated with DMBA only and group II received DMBA at age 50 and in addition, a daily intraperitoneal injection of 100 IU hCG for days 21-81 post carcinogen administration. Tumorigenic response was evaluated by biweekly palpation of all animals and by complete autopsy 24 weeks after DMBA treatment. Group I animals developed an incidence of 100% of both tumours and adenocarcinomas. Group II animals developed a significantly lower incidence of tumours and adenocarcinomas, 51.5% and 45.5% respectively. In both groups lesions developed more frequently in thoracic than in abdominal mammary glands. It is postulated that hCG treatment, probably through stimulation of ovarian oestrogen and progesterone synthesis, induces differentiation of mammary epithelium that although affected by the carcinogen can still be rescued from malignant transformation.
MeSH Terms
9,10-Dimethyl-1,2-benzanthracene
Animals
Body Weight/drug effects
Chorionic Gonadotropin/therapeutic use
Endocrine Glands/drug effects
Estrus/drug effects
Female
Humans
Mammary Glands, Animal/drug effects
Mammary Neoplasms, Experimental/chemically induced,prevention & control
Rats
Rats, Inbred Strains
Chemicals
Chorionic Gonadotropin
9,10-Dimethyl-1,2-benzanthracene
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Russo I H
Department of Pathology, Michigan Cancer Foundation, Detroit 48201.
Koszalka M
Gimotty P A
Russo J
References (29)
29 references, click to expand
-
Effect of increasing doses of estrogen and progesterone on mammary carcinogenesis in the rat.
Eur J Cancer. 1973 Jul;9(7):483-6
PMID: 4803225
-
Transiently elevated levels of c-fos and c-myc oncogene messenger ribonucleic acids in cultured murine Leydig tumor cells after addition of human chorionic gonadotropin.
Mol Endocrinol. 1989 Jan;3(1):105-9
PMID: 2536888
-
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):1451-9
PMID: 102857
-
Differentiation of the mammary gland and susceptibility to carcinogenesis.
Breast Cancer Res Treat. 1982;2(1):5-73
PMID: 6216933
-
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):721-36
PMID: 112872
-
Comparative study of human and rat mammary tumorigenesis.
Lab Invest. 1990 Mar;62(3):244-78
PMID: 2107367
-
From pathogenesis to hormone prevention of mammary carcinogenesis.
Cancer Surv. 1986;5(3):649-70
PMID: 3107814
-
Human chorionic gonadotropin stimulates proliferation of Nb 2 rat lymphoma cells.
J Clin Endocrinol Metab. 1983 May;56(5):1068-70
PMID: 6187762
-
Mammary-tumour incidence in Sprague-Dawley rats treated with 7,12-dimethylbenz(a)anthracene: effect of pregnancy and lack of effect of unilateral lactation.
Br J Cancer. 1981 Sep;44(3):451-5
PMID: 6793056
-
Changes in ovarian steroidogenesis in prepuberal rats induced to ovulate by low doses of human chorionic gonadotrophin.
J Endocrinol. 1985 Oct;107(1):113-9
PMID: 4045348
-
Effect of ovarian hormones on the induction of 1-methyl-1-nitrosourea-induced mammary cancer.
Carcinogenesis. 1983;4(4):495-7
PMID: 6839422
-
Actions of oestrogens and antioestrogens on rat mammary gland development: relevance to breast cancer prevention.
J Steroid Biochem. 1988;30(1-6):95-103
PMID: 3386282
-
Extinction of experimental mammary cancer. I. Estradiol-17beta and progesterone.
Proc Natl Acad Sci U S A. 1962 Mar 15;48:379-86
PMID: 14449778
-
EFFECT OF PREGNANCY AND LACTATION ON GROWTH OF MAMMARY TUMOURS INDUCED BY 7,12-DIMETHLBENZ(A) ANTHRACENE (DMBA).
Br J Cancer. 1965 Mar;19:160-6
PMID: 14289051
-
Biological and molecular bases of mammary carcinogenesis.
Lab Invest. 1987 Aug;57(2):112-37
PMID: 3302534
-
Effect of human chorionic gonadotrophin on 7,12-dimethylbenz[a]anthracene-induced DNA binding and repair synthesis by rat mammary epithelial cells.
Chem Biol Interact. 1985 Oct;55(1-2):13-21
PMID: 3933840
-
Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor.
Science. 1984 Nov 30;226(4678):1080-2
PMID: 6093261
-
Mammary carcinogenesis by 3-methylcholanthrene. II. Inhibitory effect of pregnancy and lactation on tumor induction.
J Natl Cancer Inst. 1960 Nov;25:991-1003
PMID: 13719701
-
Mammary cancer induced by a single feeding of polymucular hydrocarbons, and its suppression.
Nature. 1961 Jan 21;189:204-7
PMID: 13716610
-
Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins.
Cancer Res. 1985 Aug;45(8):3415-43
PMID: 3926298
-
Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland to carcinogenesis.
Cancer Res. 1980 Aug;40(8 Pt 1):2677-87
PMID: 7388818
-
Leydig cell hyperplasia due to a testicular embryonal carcinoma producing human chorionic gonadotropin.
Andrologia. 1984 Mar-Apr;16(2):146-55
PMID: 6204557
-
N-nitroso-N-methylurea-induced mammary carcinogenesis: effect of pregnancy on preneoplastic cells.
J Natl Cancer Inst. 1983 Sep;71(3):625-8
PMID: 6577237
-
N-nitrosomethylurea as mammary gland carcinogen in rats.
J Natl Cancer Inst. 1975 Feb;54(2):401-14
PMID: 1113323
-
An inverse relationship between inhibin and follicle-stimulating hormone during the period of ovulation induced by human chorionic gonadotrophin in dioestrous rats.
J Endocrinol. 1983 Jun;97(3):313-8
PMID: 6408212
-
Regulation of the synthesis of human chorionic gonadotrophin by 5-bromo-2'-deoxyuridine and dibutyryl cyclic AMP in trophoblastic and nontrophoblastic tumor cells.
J Clin Endocrinol Metab. 1978 Jul;47(1):46-51
PMID: 233662
-
Mammary carcinogenesis by 3-methylcholanthrene. I. Hormonal aspects in tumor induction and growth.
J Natl Cancer Inst. 1959 Sep;23:567-85
PMID: 13814056
-
Suppression by pregnancy of chemically induced preneoplastic cells of the rat mammary gland.
Anticancer Res. 1986 Nov-Dec;6(6):1395-400
PMID: 3101578
-
Basis of cellular autonomy in the susceptibility to carcinogenesis.
Toxicol Pathol. 1983;11(2):149-66
PMID: 6443045