Advertisement

Neoplasms of the skin and other organs observed in Swiss mice treated with nitrosoalkylureas

  • William Lijinsky
  • Melvin D. Reuber
Original Papers Experimental Oncology

Summary

A number of nitrosoalkylureas, nitrosoalkylcarbamates, and chlorinated nitrosotrialkylureas were painted twice a week on the skin of female Swiss mice at a concentration of 40 mM. Of the 29 compounds, 16 induced skin tumors in 4 or more of 20 mice; 9 compounds produced tumors in 10 or more mice. Most of the skin tumors were squamous cell or basal cell carcinomas, and some sarcomas. These carcinomas and sarcomas of the skin were large, invasive, and in several animals there were multiple large metastases to the lungs and lymph nodes. Treatment with several of the compounds was associated with poor survival. The median survival in many other groups was reduced considerably below the 2-year survival of acetone-treated controls. Many of the treatments led to development of tumors of internal organs, including mammary carcinomas, adenocarcinomas and squamous cell carcinomas of the lung, and tumors of the stomach. The stomach tumors might have arisen through exposure to the compound licked from the skin. It appears that several of the compounds were absorbed through the skin of the mice and exerted their effect systemically.

Key words

Neoplasm Swiss mice Nitrosoalkylurea 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andrews AW, Lijinsky W (1984) Mutagenicity of N-nitroso compounds in the Salmonella assay. In: Rao TK et al. (ed) Genotoxicology of N-nitroso compounds. Plenum, New York, pp 13–43Google Scholar
  2. Frei JV (1970) Toxicity, tissue changes, and tumor induction in inbred Swiss mice by methylnitrosamine and-amide compounds. Cancer Res 30:11–17PubMedGoogle Scholar
  3. Graffi A, Hoffmann F, Schütt M (1967) N-Methyl-N-nitrosourea as a strong topical carcinogen when painted on skin of rodents. Nature 214:611Google Scholar
  4. Lijinsky W (1982) Comparison of the carcinogenic effectiveness in mouse skin of methyl- and ethyl-nitrosourea, nitrosourethane and nitrosonitroguanidine and the effect of deuterium labeling. Carcinogenesis 3:1289–1291PubMedGoogle Scholar
  5. Lijinsky W (1984) Structure-activity relations in carcinogenesis by N-nitroso compounds. In: Rao TK et al. (ed) Genotoxicology of N-nitroso compounds. Plenum, New York, pp 189–231Google Scholar
  6. Lijinsky W, (1988) Structure-activity relations in carcinogenesis by N-nitroso compounds. Cancer Metastasis Rev 6:301–356Google Scholar
  7. Lijinsky W, Reuber MD (1983) Carcinogenicity of hydroxylated alkylnitrosoureas and of nitrosooxazolidones by mouse skin painting and by gavage in rats. Cancer Res 43:214–221PubMedGoogle Scholar
  8. Lijinsky W, Reuber MD (1982) Studies of a deuterium isotope effect in carcinogenesis by N-nitroso-N_alkylurethanes in rats. Cancer Lett 16:273–279CrossRefPubMedGoogle Scholar
  9. Lijinsky W, Taylor HW (1979) Carcinogenicity of chlorinated nitrosotrialkylureas in rats. J Cancer Res Clin Oncol 94:131–137PubMedGoogle Scholar
  10. Lijinsky W, Winter C (1981) Skin tumors induced by painting nitrosoalkylureas on mouse skin. J Cancer Res Clin Oncol 102:13–20PubMedGoogle Scholar
  11. Lijinsky W, Losikoff AM, Sansone EP (1981) N-Nitrosodiethanolamine and N-nitrosomorpholine readily penetrate rat skin. J Natl Cancer Inst 66:125–127PubMedGoogle Scholar
  12. Lijinsky W, Elespuru RK, Andrews AW (1987) Relative mutagenic and prophage-inducing effects of mono- and dialkylnitrosoureas. Mutat Res 178:157–165PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • William Lijinsky
    • 1
  • Melvin D. Reuber
    • 1
  1. 1.NCI-Frederick Cancer Research FacilityBRI-Basic Research ProgramFrederickUSA

Personalised recommendations