Summary
In addition to spontaneous uterine endometrial adenocarcinomas at a high incidence (35.1 %), development of endometrial hyperplasia/adenoma was also frequently detected in rats of the Donryu strain. The total yield of all observed proliferative endometrial lesions was very high (60.6%). The tumors arose commonly in the uterine horn of aged rats. Histologically, most demonstrated glandular structures, consisting of cuboidal or columnar cells with weak eosinophilic or basophilic cytoplasm ↭d large nuclei. In about half of the animals with adenocarcinomas, metastasis to remote organs such as the lung was observed. Histological examination of the ovary and vaginal epithelium revealed ovarian cysts, atrophy of the ovary and cornification of the vaginal epithelium more frequently in rats with endometrial carcinomas than in animals without tumors. These findings indicate that adenocarcinoma development in Donryu rats is associated with endocrine imbalance [increased serum estrogen: progesterone (E2∶P)ratios]. By comparative investigation of strain differences, it was confirmed that irregular estrous cycles began earlier with higher incidence in Donryu rats than in F344 rats, a low-incidence strain. Histological findings of the ovary and vaginal epithelium also suggested relatively increased estrogen levels in Donryu rats compared to F344 rats. Estimated plasma values of gonad steroids showed that the E2∶P ratio in Donryu rats at 12 months of age was about five times that in F344 rats. These results therefore indicate that hormone imbalance, particularly an increased E2∶P ratio, may play an important role in the spontaneous occurrence of endometrial adenocarcinoma in Donryu rats.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- E2/P:
-
estrogen/progesterone ratio
References
Baba N, von Haam E (1976) Tumours of the vagina, uterus, placenta and oviduct. In: Turusov VS (ed) Pathology of tumours in laboratory animals: vol 1. Tumours of the rat (part 2). IARC, Lyon, pp 161–188
Barnes AE, Crissman JD, Azoury RS, Schneider DP (1981) Association of a prolactin secreting pituitary microadenoma and endometrial carcinoma. Obstet Gynecol 58:391–394
Deerberg F, Kaspareit J (1987) Endometrial carcinoma in BDII/ Han rats: Model of a spontaneous hormone-dependent tumor. J Natl Cancer Inst 78:1245–1251
Deerberg F, Rehm S, Pittermann W (1981) Uncommon frequency of adenocarcinomas of the uterus in virgin Han:Wistar rats. Vet Pathol 18:707–713
Dockerty MB, Mussey E (1951) Malignant lesions of the uterus associated with estrogen-producing ovarian tumors. Am J Obstet Gynecol 61:147–153
Fox H (1984) Endometrial carcinogenesis and its relation to oestrogens. Pathol Res Pract 179:13–19
Futterweit W (1984) In: Futterweit W (ed) Polycystic ovarian disease. Springer, New York Berlin Heidelberg Tokyo, pp 91–92
Gardner WU, Ferrigno M (1956) Unusual neoplastic lesions of the uterine horns of estrogen-treated mice. J Natl Cancer Inst 17:601–613
Goodman DG, Hildebrandt PK (1987) Adenocarcinoma, endometrium, rat. In: Jones TC, Mohr U, Hunt RD (eds) Genital system (Monograph on pathology of laboratory animals). Springer, Berlin Heidelberg, pp 80–82
Goodman DG, Ward JM, Squire RA, Chu KC, Linhart MS (1979) Neoplastic and non-neoplastic lesions in aging F344 rats. Toxicol Appl Pharmacol 48:237–248
Gottardis M, Verdeal KM, Ertürk E, Rose DP (1982) Effect of progesterone administration on rat endometrial disease after exposure toN-nitrosomethylurea. Eur J Cancer Clin Oncol 18:1395–1396
Griffith CT, Tomic M, Craig JM, Kistner RW (1963) Effect of progestins, estrogens and castration on induced endometrial carcinoma in the rabbit. Surg Forum 14:399–401
Gusberg SB, Kaplan AL (1963) Precursors of corpus cancer IV. Adenomatous hyperplasia as stage 0 carcinoma of the endometrium. Am J Obstet Gynecol 87:662–678
Hilliard GD, Norris HJ (1979) Pathologic effects of oral contraceptives. Recent Results Cancer Res 66:49–71
Imai K, Yoshimura S (1988) Spontaneous tumors in Sprague-Dawley (CD:Crj) rats (in Japanese) J Toxicol Pathol 1:7–12
Lingeman CH (1979) Hormones and hormonomimetic compounds in the etiology of cancer. Recently Results Cancer Res 66:1–48
Maekawa A, Kurokawa Y, Takahashi M, Kokubo T, Ogiu T, Onodera H, Tanigawa H, Ohno Y, Furukawa F, Hayashi Y (1983) Spontaneous tumors in F344/DuCrj rats. Gann 74:365–372
Maekawa A, Ogiu T, Matsuoka C, Onodera H, Furuta K, Kurokawa Y, Takahashi M, Kokubo T, Tanigawa H, Hayashi Y, Nakadate M, Tanimura A (1984) Carcinogenicity of low doses ofN-ethyl-N-nitrosourea in F344 rats; a dose-response study. Gann 75:117–125
Maekawa A, Onodera H, Tanigawa H, Furuta K, Kanno J, Matsuoka C, Ogiu T, Hayashi Y (1986a) Lack of carcinogenicity of triethanolamine in F344 rats. J Toxicol Environ Health 19:345–357
Maekawa A, Onodera H, Tanigawa H, Furuta K, Matsuoka C, Kanno J, Ogiu T, Hayashi Y (1986b) Spontaneous neoplastic and non-neoplastic lesions in aging Donryu rats. Gann 77:882–890
Maekawa A, Matsuoka C, Onodera H, Tanigawa H, Furuta K, Kanno J, Jang JJ, Hayashi Y (1987a) Lack of carcinogenicity of tartrazine (FD & C yellow no.5) in the F344 rat. Food Chem Toxicol 25:891–896
Maekawa A, Onodera H, Tanigawa H, Furuta K, Kanno J, Matsuoka C, Ogiu T, Hayashi Y (1987b) Long-term studies on carcinogenicity and promoting effect of phenylbutazone in Donryu rats. J Natl Cancer Inst 79:577–584
Meissner WA, Sommers SC, Sherman G (1957) Endometrial hyperplasia, endometrial carcinoma, and endometriosis produced experimentally by estrogen. Cancer 10:500–509
Morikawa S, Sekiya S, Naitoh M, Iwasawa H, Takeda B, Takamizawa H (1982) Spontaneous occurrence of atypical hyperplasia and adenocarcinoma of the uterus in androgen-sterilized SD rats. J Natl Cancer Inst 69:95–101
Muñoz N, Dunn TB, Turusov VS (1979) Tumours of the vagina and uterus. In: Turusov VS (ed) Pathology of tumours in laboratory animals: vol 2. Tumours of the mouse. IARC, Lyon, pp 359–370
Solleveld HA, Haseman JK, McConnell (1984) Natural history of body weight gain, survival, and neoplasia in the F344 rat. J Natl Cancer Inst 72:929–940
Thompson SW, Huseby RA, Fox MA, Davis CL, Hunt RD (1961) Spontaneous tumors in the Sprague-Dawley rat. J Natl Cancer Inst 27:1037–1057
Verdeal K, Erturk E, Rose DP (1986) Endometrial adenomatous hyperplasia and carcinoma and multiple endocrinopathies in rats exposed toN-nitrosomethylurea. Anticancer Res 6:5–10
Zeil HK (1982) Estrogen's role in endometrial cancer. Obstet Gynecol 60:509–515
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nagaoka, T., Onodera, H., Matsushima, Y. et al. Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance. J Cancer Res Clin Oncol 116, 623–628 (1990). https://doi.org/10.1007/BF01637084
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01637084