Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1980 Feb;41(2):285–294. doi: 10.1038/bjc.1980.41

Induction of kidney tumours by a single dose of dimethylnitrosamine: dose response and influence of diet and benzo(a)pyrene pretreatment.

P F Swann, D G Kaufman, P N Magee, R Mace
PMCID: PMC2010195  PMID: 7370168

Abstract

Seven days on a protein-free diet increases the susceptibility of rats to the action of DMN as a renal carcinogen. The dose response for the induction of kidney tumours by a single dose of dimethylnitrosamine (DMN) in these rats is reported. The first tumour was not found until 28 weeks after the dose. At 100 weeks the incidence ranged from 22.5% at the lowest dose (20 mg/kg) to 97% at the highest dose (60 mg/kg). The incidence in probits at any time between 50 and 100 weeks was linearly related to the log dose. Epithelial and mesenchymal tumours were produced in an approximate ratio of 2:1. The protein-free diet alters the rate of metabolism of DMN in the rat, and increases the alkylation of nucleic acids by this carcinogen in the kidney. Further treatment of the rat with benzo(a)pyrene can reverse, to some extent, the change in metabolism, but does not reverse the change in alkylation. It is shown that the change in kidney-tumour incidence produced by the change in diet, and by the treatment with benzo(a)pyrene, corresponds to the changes these treatments produce in the alkylation of kidney DNA by the carcinogen.

Full text

PDF
285

Selected References

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

  1. BARNES J. M., MAGEE P. N. Some toxic properties of dimethylnitrosamine. Br J Ind Med. 1954 Jul;11(3):167–174. doi: 10.1136/oem.11.3.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barrett J. C., Ts'o P. O. Evidence for the progressive nature of neoplastic transformation in vitro. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3761–3765. doi: 10.1073/pnas.75.8.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DRUCKREY H., STEINHOFF D., PREUSSMANN R., IVANKOVIC S. ERZEUGUNG VON KREBS DURCH EINE EINMALIGE DOSIS VON METHYLNITROSO-HARNSTOFF UND VERSCHIEDENEN DIALKYLNITROSAMINEN AN RATTEN. Z Krebsforsch. 1964 Feb 7;66:1–10. [PubMed] [Google Scholar]
  4. Druckrey H., Schagen B., Ivankovic S. Erzeugung neurogener Malignome durch einmalige Gabe von Athyl-nitrosoharnstoff (ANH) an neugeborene und junge BD IX-Ratten. Z Krebsforsch. 1970;74(2):141–161. [PubMed] [Google Scholar]
  5. Hard G. C., Borland R. Morphologic character of transforming renal cell cultures derived from Wistar rats given dimethylnitrosamine. J Natl Cancer Inst. 1977 May;58(5):1377–1382. doi: 10.1093/jnci/58.5.1377. [DOI] [PubMed] [Google Scholar]
  6. Hard G. C., Butler W. H. Cellular analysis of renal neoplasia: induction of renal tumors in dietary-conditioned rats by dimethylnitrosamine, with a reappraisal of morphological characteristics. Cancer Res. 1970 Nov;30(11):2796–2805. [PubMed] [Google Scholar]
  7. Hard G. C., Butler W. H. Ultrastructural study of the development of interstitial lesions leading to mesenchymal neoplasia induced in the rat renal cortex by dimethylnitrosamine. Cancer Res. 1971 Mar;31(3):337–347. [PubMed] [Google Scholar]
  8. Hard G. C. Histological conformity of implantation tumors produced by kidney cell lines derived from dimethylnitrosamine-treated rats, with dimethylnitrosamine-induced renal mesenchymal tumors. Cancer Res. 1978 Jul;38(7):1974–1978. [PubMed] [Google Scholar]
  9. Laerum O. D., Rajewsky M. F. Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. J Natl Cancer Inst. 1975 Nov;55(5):1177–1187. doi: 10.1093/jnci/55.5.1177. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. McLean A. E., Magee P. N. Increased renal carcinogenesis by dimethyl nitrosamine in protein deficient rats. Br J Exp Pathol. 1970 Dec;51(6):587–590. [PMC free article] [PubMed] [Google Scholar]
  12. McLean A. E., McLean E. K. The effect of diet and 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) on microsomal hydroxylating enzymes and on sensitivity of rats to carbon tetrachloride poisoning. Biochem J. 1966 Aug;100(2):564–571. doi: 10.1042/bj1000564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McLean A. E., Verschuuren H. G. Effects of diet and microsomal enzyme induction on the toxicity of dimethyl nitrosamine. Br J Exp Pathol. 1969 Feb;50(1):22–25. [PMC free article] [PubMed] [Google Scholar]
  14. Roscoe J. P., Claisse P. J. Analysis of N-ethyl-N-nitrosourea-induced brain carcinogenesis by sequential culturing during the latent period. I. Morphology and tumorigenicity of the cultured cells and their growth in agar. J Natl Cancer Inst. 1978 Aug;61(2):381–390. [PubMed] [Google Scholar]
  15. Stewart B. W., Magee P. N. Modification of dimethylnitrosamine-induced changes in renal metabolism and subsequent effect on carcinogenic activity of actinomycin D and cycloheximide. Eur J Cancer. 1973 Jan;9(1):37–47. doi: 10.1016/0014-2964(73)90041-8. [DOI] [PubMed] [Google Scholar]
  16. Swann P. F., McLean A. E. Cellular injury and carcinogenesis. The effect of a protein-free high-carbohydrate diet on the metabolism of dimethylnitrosamine in the rat. Biochem J. 1971 Sep;124(2):283–288. doi: 10.1042/bj1240283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Swenberg J. A., Koestner A., Wechsler W., Denlinger R. H. Quantitative aspects of transplacental tumor induction with ethylnitrosourea in rats. Cancer Res. 1972 Dec;32(12):2656–2660. [PubMed] [Google Scholar]
  18. Waynforth H. B., Parkin R., Stoddart D. J. The effect of a protein-free diet, a sugar diet and of carbon tetrachloride administration on the toxicity and rate of metabolism of dimethylnitrosamine in different rat strains. Br J Exp Pathol. 1977 Apr;58(2):225–229. [PMC free article] [PubMed] [Google Scholar]
  19. Wodinsky I., Helinski A., Kensler C. J. Experimental tumorigenesis in the hamster cheek pouch. Nature. 1965 Aug 14;207(998):770–772. doi: 10.1038/207770b0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES