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. 1986 Sep;68:81–89. doi: 10.1289/ehp.866881

Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies.

J M Ward, R Quander, D Devor, M L Wenk, E F Spangler
PMCID: PMC1474263  PMID: 3780636

Abstract

The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors included histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Astrup E. G., Iversen O. H., Elgjo K. The tumorigenic and carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of BALB/cA mice. Virchows Arch B Cell Pathol Incl Mol Pathol. 1980;33(3):303–304. [PubMed] [Google Scholar]
  3. Astrup E. G., Iversen O. H. The tumourigenic and carcinogenic effect of 12-0-tetradecanoylphorbol-13-acetate when applied to the skin of BALB/cA and hairless (hr/hr) mice. Acta Pathol Microbiol Immunol Scand A. 1983 Mar;91(2):103–113. doi: 10.1111/j.1699-0463.1983.tb02734.x. [DOI] [PubMed] [Google Scholar]
  4. BIELSCHOWSKY F., BIELSCHOWSKY M. The New Zealand strain of obese mice; their response to stilboestrol and to insulin. Aust J Exp Biol Med Sci. 1956 Jun;34(3):181–198. doi: 10.1038/icb.1956.22. [DOI] [PubMed] [Google Scholar]
  5. BOUTWELL R. K. SOME BIOLOGICAL ASPECTS OF SKIN CARCINOGENISIS. Prog Exp Tumor Res. 1964;4:207–250. doi: 10.1159/000385978. [DOI] [PubMed] [Google Scholar]
  6. DiGiovanni J., Slaga T. J., Boutwell R. K. Comparison of the tumor-initiating activity of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene in female SENCAR and CS-1 mice. Carcinogenesis. 1980 May;1(5):381–389. doi: 10.1093/carcin/1.5.381. [DOI] [PubMed] [Google Scholar]
  7. Diwan B. A., Ward J. M., Henneman J., Wenk M. L. Effects of short-term exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in SENCAR mice. Cancer Lett. 1985 Mar;26(2):177–184. doi: 10.1016/0304-3835(85)90024-2. [DOI] [PubMed] [Google Scholar]
  8. Diwan B. A., Ward J. M., Rice J. M., Colburn N. H., Spangler E. F. Tumor-promoting effects of di(2-ethylhexyl)phthalate in JB6 mouse epidermal cells and mouse skin. Carcinogenesis. 1985 Mar;6(3):343–347. doi: 10.1093/carcin/6.3.343. [DOI] [PubMed] [Google Scholar]
  9. Frith C. H., Davis T. M., Zolotor L. A., Townsend J. W. Histiocytic lymphoma in the mouse. Leuk Res. 1980;4(6):651–662. doi: 10.1016/0145-2126(80)90076-4. [DOI] [PubMed] [Google Scholar]
  10. Hennings H., Devor D., Wenk M. L., Slaga T. J., Former B., Colburn N. H., Bowden G. T., Elgjo K., Yuspa S. H. Comparison of two-stage epidermal carcinogenesis initiated by 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine in newborn and adult SENCAR and BALB/c mice. Cancer Res. 1981 Mar;41(3):773–779. [PubMed] [Google Scholar]
  11. Homburger F., Russfield A. B., Weisburger J. H., Lim S., Chak S. P., Weisburger E. K. Aging changes in CD-1 HaM/ICR mice reared under standard laboratory conditions. J Natl Cancer Inst. 1975 Jul;55(1):37–45. doi: 10.1093/jnci/55.1.37. [DOI] [PubMed] [Google Scholar]
  12. Kripke M. L. Immunologic mechanisms in UV radiation carcinogenesis. Adv Cancer Res. 1981;34:69–106. doi: 10.1016/s0065-230x(08)60239-0. [DOI] [PubMed] [Google Scholar]
  13. Markham R. V., Jr, Sutherland J. C., Mardiney M. R., Jr The ubiquitous occurrence of immune complex localization in the renal glomeruli of normal mice. Lab Invest. 1973 Jul;29(1):111–120. [PubMed] [Google Scholar]
  14. Ohshima M., Ward J. M., Wenk M. L. Preventive and enhancing effects of retinoids on the development of naturally occurring tumors of skin, prostate gland, and endocrine pancreas in aged male ACI/segHapBR rats. J Natl Cancer Inst. 1985 Feb;74(2):517–524. [PubMed] [Google Scholar]
  15. Outzen H. C. Development of carcinogen-induced skin tumors in mice with varied states of immune capacity. Int J Cancer. 1980 Jul 15;26(1):87–92. doi: 10.1002/ijc.2910260114. [DOI] [PubMed] [Google Scholar]
  16. Percy D. H., Jonas A. M. Incidence of spontaneous tumors in CD (R) -1 HaM-ICR mice. J Natl Cancer Inst. 1971 May;46(5):1045–1065. [PubMed] [Google Scholar]
  17. Slaga T. J., Klein-Szanto A. J., Triplett L. L., Yotti L. P., Trosko K. E. Skin tumor-promoting activity of benzoyl peroxide, a widely used free radical-generating compound. Science. 1981 Aug 28;213(4511):1023–1025. doi: 10.1126/science.6791284. [DOI] [PubMed] [Google Scholar]
  18. Slaga T. J. Overview of tumor promotion in animals. Environ Health Perspect. 1983 Apr;50:3–14. doi: 10.1289/ehp.83503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stewart H. L., Deringer M. K., Dunn T. B., Snell K. C. Malignant schwannomas of nerve roots, uterus, and epididymis in mice. J Natl Cancer Inst. 1974 Dec;53(6):1749–1758. [PubMed] [Google Scholar]
  20. Strickland P. T. Tumor induction in Sencar mice in response to ultraviolet radiation. Carcinogenesis. 1982;3(12):1487–1489. doi: 10.1093/carcin/3.12.1487. [DOI] [PubMed] [Google Scholar]
  21. Van Duuren B. L., Sivak A., Katz C., Seidman I., Melchionne S. The effect of aging and interval between primary and secondary treatment in two-stage carcinogenesis on mouse skin. Cancer Res. 1975 Mar;35(3):502–505. [PubMed] [Google Scholar]
  22. Ward J. M., Argilan F., Reynolds C. W. Immunoperoxidase localization of large granular lymphocytes in normal tissues and lesions of athymic nude rats. J Immunol. 1983 Jul;131(1):132–139. [PubMed] [Google Scholar]
  23. Ward J. M., Goodman D. G., Squire R. A., Chu K. C., Linhart M. S. Neoplastic and nonneoplastic lesions in aging (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice. J Natl Cancer Inst. 1979 Sep;63(3):849–854. doi: 10.1093/jnci/63.3.849. [DOI] [PubMed] [Google Scholar]
  24. Ward J. M., Rehm S., Devor D., Hennings H., Wenk M. L. Differential carcinogenic effects of intraperitoneal initiation with 7,12-dimethylbenz(a)anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice. Environ Health Perspect. 1986 Sep;68:61–68. doi: 10.1289/ehp.866861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ward J. M., Singh G., Katyal S. L., Anderson L. M., Kovatch R. M. Immunocytochemical localization of the surfactant apoprotein and Clara cell antigen in chemically induced and naturally occurring pulmonary neoplasms of mice. Am J Pathol. 1985 Mar;118(3):493–499. [PMC free article] [PubMed] [Google Scholar]

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