Sequential Functional and Morphological Alterations During Hepatocarcinogenesis Induced in Rats by Feeding of a Low Dose of 2-Acetylaminofluorene

Stenbäck, Frej; Gebhardt, Rolf; Sirma, Hussein; Garbay, Jean-Marc; Williams, Gary M.

doi:10.1177/019262339402200606

Cited by 12 publications

(4 citation statements)

References 28 publications

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“…Endpoints were analyzed weekly. The data agree essentially with those from our Wistar rats, but doses overlapped only partially, and Stenbäck et al (1994) interpret the results differently than we did. They did not observe necroses and apoptoses and therefore consider these doses not to be toxic.…”

Section: Dose-response Relationshipssupporting

confidence: 79%

“…In contrast to the opinion of Enzmann and Bannasch (1988), who related the elimination of early and severely altered foci after cessation of AAF exposure to unspecific toxic effects, Stenbäck et al (1994) propose that foci disappear due to remodeling-that is, they regain a normal phenotype due to homeostatic influences of the neighboring hepatocytes. In their final remarks the authors emphasized that the dose was low in these experiments and toxic effects could not have contributed.…”

Section: Promotion-morphological Alterationsmentioning

confidence: 64%

“…One of the few studies in which rats were treated chronically with AAF without additional promoter or partial hepatectomy was also performed in Williams's laboratory (Stenbäck et al, 1994). Male Fisher rats received 200 ppm (0.02%) AAF for 10 weeks, or for 8 weeks with a 24-week observation period.…”

Section: Dose-response Relationshipsmentioning

confidence: 99%

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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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Section: Dose-response Relationshipssupporting

confidence: 79%

Section: Promotion-morphological Alterationsmentioning

confidence: 64%

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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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“…Similarly, for other transferases (329,330), DNA adduct formation (331), or other mechanistic aspects of carcinogenesis (332), this compound is the model. Data from the ED 01 study, where about 25,000 mice were given 2-AAF at various levels, have yielded many papers; the data are still being reexamined (333)(334)(335)(336). Various reviews on 2-AAF have appeared (34,337,338), but realistically the number of papers on 2-AAF and its derivatives (approximately 125 in 5 years) is so large that a review every 5 years or so would be needed to keep research personnel informed.…”

Section: Toxic Effectsmentioning

confidence: 99%

Aromatic Nitro and Amino Compounds

Bingham¹,

McGowan²

2012

Patty's Toxicology

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Logically, aromatic nitro and amino compounds should be discussed together because their toxic responses are often similar due to a common metabolic intermediate. Synthetically, amines are generally derived from nitro compounds, but in some cases nitro compounds can be prepared through amines when other methods fail to afford specific compounds. There are good and bad attributes to these types of compounds. Some act as sensitizers and contingent on physical properties may be absorbed through the skin or mucous membranes. They may also cause methemoglobinemia, depending on such factors as the structure and the particular organism. Some members of this class are known as animal and human carcinogens; for humans, the urinary bladder is the most prominent target organ. Nevertheless, these compounds and their derivatives have enlivened our world through their use as dyestuff intermediates or as photographic chemicals, they alleviate pain as components of widely used analgesics, and they cushion or insulate us through their use in flexible and rigid foams. Other important uses include production of pesticides, including herbicides and fungicides, as ingredients in adhesives, paints and coatings, antioxidants, explosives, optical brighteners, rubber ingredients, and as intermediates in many other products.

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Aromatic Nitro and Amino Compounds

Johnson¹

2023

Patty's Toxicology

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Aromatic nitro and amino compounds have various commercial, governmental, and public applications. Their uses include manufacturing of dyes, pesticides, drugs, and explosives. These substances are typically considered high‐nitrogen compounds and as such share many of the same chemical and biological properties. Many have amines and/or nitrate groups on the ring and because of this exhibit properties where they are not highly water or lipid soluble and many tend to form crystals. When released to the environment, nitrate‐containing moieties are often reduced to amines by bacteria in wet soils and sediments. Acute effects typically target the nervous system; however, sublethal effects from repetitive exposures include anemia, methemoglobinemia, and often male reproductive effects. Cyanosis has been described from relatively high repetitive exposures. Oral exposures can affect the liver. Many are absorbed through the skin where dermal exposures can significantly contribute to systemic dose. Skin sensitization and irritation have been observed from exposure to some compounds. Many are eliminated via the urine; however, conjugated metabolites can be eliminated via the feces. Nitroso metabolites are suspected as having influence in observation of cancer, particularly in the bladder. Other similar nitramine compounds are also briefly described.

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Sequential Functional and Morphological Alterations During Hepatocarcinogenesis Induced in Rats by Feeding of a Low Dose of 2-Acetylaminofluorene

Cited by 12 publications

References 28 publications

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

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

Aromatic Nitro and Amino Compounds

Aromatic Nitro and Amino Compounds

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