Cancer Letters

Cancer Letters

Volume 26, Issue 2, March 1985, Pages 171-176
Cancer Letters

Research letter
Stage dependent enhanced induction of hepatocellular carcinomas in rats administered a second dose of diethylnitrosamine

https://doi.org/10.1016/0304-3835(85)90023-0Get rights and content

Abstract

An experiment was performed to investigate whether the incidence of chemical carcinogen-induced liver tumors in rats is increased by administration, during promotion, of a second dose of carcinogen. Seven groups of male Fischer-344 rats were administered a dose of diethylnitrosamine (DEN), and were placed, 1 month thereafter, on a liver-tumor promotion-regimen, consisting of a choline-devoid diet containing 0.06% phenobarbital. A second dose of the carcinogen was administered, at monthly intervals of promotion, to some of the groups of animals. The experiment was terminated after 7 months of promotion, and the incidence of hepatic tumors was determined histopathologically. In rats administered the second dose of carcinogen after 2 months of promotion, the incidence of hepatocellular carcinomas was 2–3 times greater than that in the other groups of rats. The results are consistent with the proposal, advanced by others, that development of hepatocellular carcinomas may be a multi-hit process, and indicate that, after the first induced at initiation, further genomic alteration(s) may have to occur at very discrete stage(s) in the evolution of initiated cells to tumors.

References (18)

  • D.Y. Lai et al.

    Dialkylnitrosamine bioactivation and carcinogenesis

    Life Sci.

    (1980)
  • T.A. Stewart et al.

    Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTVmyc fusion genes

    Cell

    (1984)
  • J. Cairns

    The origin of human cancers

    Nature

    (1981)
  • E. Farber

    The biochemistry of preneoplastic liver: a common metabolic pattern in hepatocyte nodules

    Can. J. Biochem. Cell Biol.

    (1984)
  • T. Goldsworthy et al.

    The natural history and dose response characteristics of enzyme-altered foci in rat liver following phenobarbital and diethylnitrosamine administration

    Carcinogenesis

    (1984)
  • H. Henning et al.

    Malignant conversion of mouse skin tumours is increased by tumor initiators and unaffected by tumor promoters

    Nature

    (1983)
  • R.M. Hicks

    Pathological and biochemical aspects of tumor promotion

    Carcinogenesis

    (1983)
  • A.G. Knudson

    Mutation and childhood cancer. A probabilistic model for the incidence of retinoblastoma

  • R. Montesano et al.

    Initiation and promotion in carcinogenesis: an appraisal

    Cancer Survey

    (1983)
There are more references available in the full text version of this article.

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