The Role of Initiating and Promoting Properties in Aromatic Amine Carcinogenesis

Neumann, Hans‐Günter

doi:10.1007/978-1-4757-9640-7_28

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…We therefore assume that AAF, in contrast to AAS, has some additional properties that create promotional pressure. We have previously collected data that sup-port this working hypothesis (4) by comparing the effects of these chemicals in the rat liver system at the biochemical and the biological level, and we now summarize some more recent results.…”

Section: Introductionmentioning

confidence: 96%

Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

Neumann

Hammerl

Hillesheim

et al. 1990

Environ Health Perspect

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It has been demonstrated in several model systems that tumors arise in a multistage process. Carcinogenic aromatic amines are complete carcinogens, which usually produce tumors in typical target tissues without any additional treatment. The tissue specificity, however, cannot readily be explained by genotoxic effects, and the role of secondary effects is not well understood. Promotional pressure on initiated cells can be produced by endogenous factors but also by the chemical itself. Comparison of the effects on rat liver of 2-acetylaminofluorene (AAF) and trans4-acetylaminostilbene (AAS) provides some evidence that initiating and promoting properties of these chemicals can be separated. AAS is a strong initiator in rat liver but seems to lack promoting activity; AAF is a less efficient initiator but has tumor promoting properties. The results obtained so far indicate that promoting pressure is not produced by the acute, cytotoxic effects of AAF. It is therefore concluded that nongenotoxic, possibly receptor-mediated effects are involved.

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Section: Introductionmentioning

confidence: 96%

Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

Neumann

Hammerl

Hillesheim

et al. 1990

Environ Health Perspect

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Impairment of respiration and oxidative phosphorylation by redox cyclers 2-nitrosofluorene and menadione

Klöhn

Neumann

1997

Chemico-Biological Interactions

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Aromatic Amines in Experimental Cancer Research: Tissue-Specific Effects, an Old Problem and New Solutions

Neumann

2007

Critical Reviews in Toxicology

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Carcinogenic aromatic amines usually produce tumors in specific target tissue, such as 2-acetylaminofluorene (AAF) producing liver tumors in rats, in contrast to some other structurally related arylamines. A hypothesis is presented that explains the mode of action in this rat liver model. Genotoxic and nongenotoxic effects work together and make AAF a complete rat liver carcinogen. The cytotoxic, promoting effects are particularly important. N-Hydroxy-2-aminofluorene and 2-nitrosofluorene, two metabolites of AAF, are able to uncouple the mitochondrial respiratory chain. They entertain a redox cycle that removes electrons from the respiratory chain and impairs ATP production. The dose-dependent opening of the mitochondrial permeability transition pore signals the viability of the cell. If the pore is opened to a certain extent, the cell is eliminated by apoptosis. As a consequence, oval cells proliferate, and as this process is overloaded, the liver transforms into a cirrhosis-like situation and thus provides the conditions under which initiated liver cells develop tumors. Such an interpretation is based on assumptions that have been debated for a long time. Some of these often forgotten developments are reviewed in support of the hypothesis, which allows a more comprehensive view of the complex in vivo situation at a time when in vitro models prevail.

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The Role of Initiating and Promoting Properties in Aromatic Amine Carcinogenesis

Cited by 3 publications

References 23 publications

Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

Role of genotoxic and nongenotoxic effects in multistage carcinogenicity of aromatic amines.

Impairment of respiration and oxidative phosphorylation by redox cyclers 2-nitrosofluorene and menadione

Aromatic Amines in Experimental Cancer Research: Tissue-Specific Effects, an Old Problem and New Solutions

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