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. 1990 Nov;116(6):623–628. doi: 10.1007/BF01637084

Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance

Takaharu Nagaoka 1, Hiroshi Onodera 1, Yuko Matsushima 1, Asahi Todate 1, Makoto Shibutani 1, Hiroyuki Ogasawara 1, Akihiko Maekawa 1,✉
PMCID: PMC12201435  PMID: 2254380

Abstract

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.

Key words: Spontaneous uterine adenocarcinoma, Donryu rat, Endocrine imbalance, Estrogen, Estrogen: progesterone ratio (E2∶P ratio)

Abbreviation

E2/P

estrogen/progesterone ratio

References

  1. 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 [PubMed] [Google Scholar]
  2. Barnes AE, Crissman JD, Azoury RS, Schneider DP (1981) Association of a prolactin secreting pituitary microadenoma and endometrial carcinoma. Obstet Gynecol 58:391–394 [PubMed] [Google Scholar]
  3. 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 [PubMed] [Google Scholar]
  4. Deerberg F, Rehm S, Pittermann W (1981) Uncommon frequency of adenocarcinomas of the uterus in virgin Han:Wistar rats. Vet Pathol 18:707–713 [DOI] [PubMed] [Google Scholar]
  5. Dockerty MB, Mussey E (1951) Malignant lesions of the uterus associated with estrogen-producing ovarian tumors. Am J Obstet Gynecol 61:147–153 [DOI] [PubMed] [Google Scholar]
  6. Fox H (1984) Endometrial carcinogenesis and its relation to oestrogens. Pathol Res Pract 179:13–19 [DOI] [PubMed] [Google Scholar]
  7. Futterweit W (1984) In: Futterweit W (ed) Polycystic ovarian disease. Springer, New York Berlin Heidelberg Tokyo, pp 91–92 [Google Scholar]
  8. Gardner WU, Ferrigno M (1956) Unusual neoplastic lesions of the uterine horns of estrogen-treated mice. J Natl Cancer Inst 17:601–613 [PubMed] [Google Scholar]
  9. 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 [Google Scholar]
  10. 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 [DOI] [PubMed] [Google Scholar]
  11. 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 [DOI] [PubMed] [Google Scholar]
  12. 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 [PubMed] [Google Scholar]
  13. 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 [PubMed] [Google Scholar]
  14. Hilliard GD, Norris HJ (1979) Pathologic effects of oral contraceptives. Recent Results Cancer Res 66:49–71 [DOI] [PubMed] [Google Scholar]
  15. Imai K, Yoshimura S (1988) Spontaneous tumors in Sprague-Dawley (CD:Crj) rats (in Japanese) J Toxicol Pathol 1:7–12 [Google Scholar]
  16. Lingeman CH (1979) Hormones and hormonomimetic compounds in the etiology of cancer. Recently Results Cancer Res 66:1–48 [DOI] [PubMed] [Google Scholar]
  17. 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 [PubMed] [Google Scholar]
  18. 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 [PubMed] [Google Scholar]
  19. 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 [DOI] [PubMed] [Google Scholar]
  20. 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 [PubMed] [Google Scholar]
  21. 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 [DOI] [PubMed] [Google Scholar]
  22. 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 [PubMed] [Google Scholar]
  23. Meissner WA, Sommers SC, Sherman G (1957) Endometrial hyperplasia, endometrial carcinoma, and endometriosis produced experimentally by estrogen. Cancer 10:500–509 [DOI] [PubMed] [Google Scholar]
  24. 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 [PubMed] [Google Scholar]
  25. 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 [Google Scholar]
  26. 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 [PubMed] [Google Scholar]
  27. 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 [PubMed] [Google Scholar]
  28. 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 [PubMed] [Google Scholar]
  29. Zeil HK (1982) Estrogen's role in endometrial cancer. Obstet Gynecol 60:509–515 [PubMed] [Google Scholar]

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