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Nongenotoxic Carcinogenesis in the Liver

  • R. Schulte-Hermann
  • W. Bursch
  • B. Grasl-Kraupp
  • W. Huber
  • W. Parzefall
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 10)

Abstract

Numerous compounds have been found to produce tumors in rodent liver but have shown no evidence of genotoxic activity. These nongenotoxic compounds comprise a diverse group of important drugs and environmental pollutants. Examples are shown in Table 1 (Schulte-Hermann 1985; Schulte-Hermann et al. 1990b). Some agents, for example, certain steroids, have been associated with tumor formation in human liver (Schulte-Hermann 1985; Schulte-Hermann et al. 1990a; Tao 1991), and ethanol can be classified as a human nongenotoxic carcinogen, too. Therefore, hepatocarcinogenesis induced by nongenotoxic agents is not only a problem in rodents, and assessment of human health risks is urgently required. For this purpose we need to know the relevant
Table 1

Some nongenotoxic hepatocarcinogens and their acute hepatic effects

Prototype

Induction of Growth

Monooxygenase

Other

Phenobarbitol

DDT, HCH, some PCB

TCDD, some PCBs

Estradiol esters

ethinylestradiol

Clofibrate, diethyl-

hexylphthalate, nafenopin

Thioacetamide

thiobenzamide

Ethanol

CCl4

+

+

+

+

+

+

+

P450 II B,C

isoforms

P450 I A

-

P450 IV

-

P450 II E1

-

+

+

Clotting factors

angiotensinogen, etc.

Some peroxisomal

enzymes

Phase II enzymes

+

DDT, dichlorodiphenyl-trichloroethane; HCH, hexachlorocyclohexane; PCB, polychlorinated biphenyls; TCDD, tetrachlorodibenzodioxin.

biological effects of these agents in rodent and human liver as well as the mechanisms underlying carcinogenesis.

Keywords

Normal Liver Cell Active Cell Death Genotoxic Carcinogen Preneoplastic Cell Preneoplastic Focus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • R. Schulte-Hermann
  • W. Bursch
  • B. Grasl-Kraupp
  • W. Huber
  • W. Parzefall

There are no affiliations available

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