Abstract
Many polycyclic aromatic amines are mutagenic, and their genotoxic properties are held responsible for their biological effects. The genotoxic effects are explained by the formation of metabolites that react with macromolecules by forming adducts (Kriek 1969; Franz et al. 1986). DNA adducts may cause mutations which are responsible for tumorigenic effects. Results from comparative studies, however, indicate that tissue-specific and species-specific tumor formation caused by arylamines cannot be explained readily by the extent of DNA modifications. Long-term feeding of 2-acetylaminofluorene (AAF) typically produces liver tumors; 2-acetylaminophenanthrene (AAP), mammary tumors; andtrans-4-acetylaminostilbene (AAS), Zymbal’s gland tumors in rats (Neumann et al. 1970). All three arylamines are genotoxic. They generate comparable DNA adduct levels in rat liver, and in liver more extensively than in any other tissue (Neumann 1983; Ruthsatz and Neumann 1988; Gupta et al. 1989). But only AAF is a complete carcinogen in rat liver. AAS and AAP are able to produce liver tumors in rats only, if initiation is followed by some promotion treatment (Hammerl 1989). Therefore, DNA binding may reflect the formation of some critical lesions related to tumor initiation but is not sufficient to explain carcinogenic effects. This raises two questions: (1) Do differences in genotoxic initiating effects contribute to tissue specificity? and (2) What are the additional promoting properties of AAF that distinguish it from the incomplete liver carcinogens?
Keywords
- Aromatic Amine
- Liver Mitochondrion
- Redox Cycling
- Respiration Control Ratio
- Ethylene Glycol Tetra Acetic Acid
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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Bitsch, A., Fecher, J., Jost, M., Klöhn, PC., Neumann, HG. (1997). Genotoxic and Chronic Toxic Effects in the Carcinogenicity of Aromatic Amines. In: Müller-Hermelink, H.K., Neumann, HG., Dekant, W. (eds) Risk and Progression Factors in Carcinogenesis. Recent Results in Cancer Research, vol 143. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60393-8_14
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