Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1974 Dec;30(6):512–523. doi: 10.1038/bjc.1974.230

The Effect of N-Nitroso-N-Methylurea and N-Dimethylnitrosamine on Cell Mediated and Humoral Immune Responses in Rats and Mice

H B Waynforth, P N Magee
PMCID: PMC2009337  PMID: 4614857

Abstract

N-Nitroso-N-methylurea (NMU) induced a marked dose dependent leucopoenia which was associated with an increased survival of skin allografts in adult rats and in 2 strains of mice. The humoral immune response to NMU as assessed by haemolytic plaque formation and haemagglutination was also much reduced. Dimethylnitrosamine (DMN) which, like NMU is a powerful carcinogen and an alkylating agent, showed no immunosuppressive activity after a single dose in rats on either a normal diet or fed a protein-free diet which enhances kidney tumourigenesis. In mice DMN at a near LD50 dose (14 mg/kg) had no effect on skin graft survival but did reduce the humoral response. At half this dose level, however, no immunosuppressive effect was seen. The results support the conclusion that the immunosuppressive activity of a chemical carcinogen is not necessarily associated with the expression of its carcinogenicity.

Full text

PDF
512

Selected References

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

  1. BERENBAUM M. C. EFFECTS OF CARCINOGENS ON IMMUNE PROCESSES. Br Med Bull. 1964 May;20:159–164. doi: 10.1093/oxfordjournals.bmb.a070311. [DOI] [PubMed] [Google Scholar]
  2. Ball J. K. Immunosuppression and carcinogenesis: contrasting effects with 7,12-dimethylbenz[a]anthracene, benz[a]pyrene, and 3-methylcholanthrene. J Natl Cancer Inst. 1970 Jan;44(1):1–10. [PubMed] [Google Scholar]
  3. Ball J. K., Sinclair N. R., McCarter J. A. Prolonged immunosuppression and tumor induction by a chemical carcinogen injected at birth. Science. 1966 Apr 29;152(3722):650–651. doi: 10.1126/science.152.3722.650. [DOI] [PubMed] [Google Scholar]
  4. Carbone G., Parmiani G. Increased oncogenic effect of a low dose of methylcholanthrene in immunodepressed mice. Tumori. 1971 Jul-Aug;57(4):225–231. doi: 10.1177/030089167105700401. [DOI] [PubMed] [Google Scholar]
  5. Denlinger R. H., Swenberg J. A., Koestner A., Wechsler W. Differential effect of immunosuppression on the induction of nervous system and bladder tumors by N-methyl N-nitrosourea. J Natl Cancer Inst. 1973 Jan;50(1):87–93. doi: 10.1093/jnci/50.1.87. [DOI] [PubMed] [Google Scholar]
  6. Doell R. G., De Vaux St Cyr C., Grabar P. Immune reactivity prior to development of thymic lymphoma in C57BL mice. Int J Cancer. 1967 Mar 15;2(2):103–108. doi: 10.1002/ijc.2910020205. [DOI] [PubMed] [Google Scholar]
  7. Druckrey H., Preussmann R., Ivankovic S., Schmähl D. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z Krebsforsch. 1967;69(2):103–201. [PubMed] [Google Scholar]
  8. Frei J. V. Toxicity, tissue changes, and tumor induction in inbred Swiss mice by methylnitrosamine and -amide compounds. Cancer Res. 1970 Jan;30(1):11–17. [PubMed] [Google Scholar]
  9. Hicks R. M., Wakefield J. S. Rapid induction of bladder cancer in rats with N-methyl-N-nitrosourea. I. Histology. Chem Biol Interact. 1972 Jul;5(2):139–152. doi: 10.1016/0009-2797(72)90040-3. [DOI] [PubMed] [Google Scholar]
  10. LINDER O. E. Survival of skin homografts in methylcholanthrene-treated mice and in mice with spontaneous mammary cancers. Cancer Res. 1962 Apr;22:380–383. [PubMed] [Google Scholar]
  11. Lappé M. A., Prehn R. T. Immunologic surveillance at the marcoscopic level: nonselective elimination of premalignant skin papillomas. Cancer Res. 1969 Dec;29(12):2374–2380. [PubMed] [Google Scholar]
  12. Lappé M. A., Prehn R. T. The predictive value of skin allograft survival times during the development of urethan-induced lung adenomas in BALB-c mice. Cancer Res. 1970 May;30(5):1357–1361. [PubMed] [Google Scholar]
  13. Lappé M. A., Steinmuller D. S. Depression of weak allograft immunity in the mouse by neonatal or adult exposure to urethan. Cancer Res. 1970 Mar;30(3):674–678. [PubMed] [Google Scholar]
  14. Leaver D. D., Swann P. F., Magee P. N. The induction of tumours in the rat by a single oral dose of N-nitrosomethylurea. Br J Cancer. 1969 Mar;23(1):177–187. doi: 10.1038/bjc.1969.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MAGEE P. N., BARNES J. M. Induction of kidney tumours in the rat with dimethylnitrosamine (N-nitrosodimethylamine). J Pathol Bacteriol. 1962 Jul;84:19–31. doi: 10.1002/path.1700840103. [DOI] [PubMed] [Google Scholar]
  16. MALMGREN R. A., BENNISON B. E., McKINLEY T. W., Jr Reduced antibody titers in mice treated with carcinogenic and cancer chemotherapeutic agents. Proc Soc Exp Biol Med. 1952 Mar;79(3):484–488. doi: 10.3181/00379727-79-19419. [DOI] [PubMed] [Google Scholar]
  17. Magee P. N., Barnes J. M. Carcinogenic nitroso compounds. Adv Cancer Res. 1967;10:163–246. doi: 10.1016/s0065-230x(08)60079-2. [DOI] [PubMed] [Google Scholar]
  18. PREHN R. T. FUNCTION OF DEPRESSED IMMUNOLOGIC REACTIVITY DURING CARCINOGENESIS. J Natl Cancer Inst. 1963 Oct;31:791–805. [PubMed] [Google Scholar]
  19. Parmiani G., Colnaghi M. I., Della Porta G. Immunodepression during urethane and N-nitrosomethylurea leukaemogenesis in mice. Br J Cancer. 1971 Jun;25(2):354–364. doi: 10.1038/bjc.1971.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parmiani G., Colnaghi M. I., Della Porta G. Immunodepressive and leukemogenic effects of urethan in C3Hf and SWR mice. Proc Soc Exp Biol Med. 1969 Mar;130(3):828–830. doi: 10.3181/00379727-130-33665. [DOI] [PubMed] [Google Scholar]
  21. Parmiani G. Immune-depressive effect of urethan on the homograft response in mice. Int J Cancer. 1970 Mar 15;5(2):260–265. doi: 10.1002/ijc.2910050214. [DOI] [PubMed] [Google Scholar]
  22. Scherf H. R. Untersuchungen an männlichen Sprague-Dawley-Ratten über Zusammenhänge zwischen der immundepressiven und der carcinogenen Wirkung bei vier N-Nitroso-Verbindungen. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1972;77(3):189–193. doi: 10.1007/BF02570684. [DOI] [PubMed] [Google Scholar]
  23. Stjernswärd J. Further immunological studies of chemical carcinogenesis. J Natl Cancer Inst. 1967 Apr;38(4):515–526. [PubMed] [Google Scholar]
  24. Stjernswärd J. Immunodepressive effect of 3-methylcholanthrene. Antibody formation at the cellular level and reaction against weak antigenic homografts. J Natl Cancer Inst. 1965 Nov;35(5):885–892. [PubMed] [Google Scholar]
  25. Stutman O. Carcinogen-induced immune depression: absence in mice resistant to chemical oncogenesis. Science. 1969 Oct 31;166(3905):620–621. doi: 10.1126/science.166.3905.620. [DOI] [PubMed] [Google Scholar]
  26. Stutman O. Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science. 1974 Feb 8;183(4124):534–536. doi: 10.1126/science.183.4124.534. [DOI] [PubMed] [Google Scholar]
  27. Swann P. F., Magee P. N. Nitrosamine-induced carcinogenesis. The alklylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem J. 1968 Nov;110(1):39–47. doi: 10.1042/bj1100039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Trainin N., Linker-Israeli M., Small M., Boiato-Chen L. Enhancement of lung adenoma formation by neonatal thymectomy in mice treated with 7,12-dimethylbenz(a)anthracene or urethan. Int J Cancer. 1967 Jul 15;2(4):326–336. doi: 10.1002/ijc.2910020407. [DOI] [PubMed] [Google Scholar]
  29. den Engelse L., Bentvelzen P. A., Emmelot P. Studies on lung tumours. I. Methylation of deoxyribonucleic acid and tumour formation following administration of dimethylnitrosamine to mice. Chem Biol Interact. 1970 Apr;1(4):395–406. doi: 10.1016/0009-2797(70)90006-2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES