Relationship of DNA Adducts Derived from 2-Acetylaminofluorene to Cell Proliferation and the Induction of Rodent Liver and Bladder Tumors

Cohen, Samuel M.; Ellwein, Leon B.

doi:10.1177/019262339502300206

Cited by 21 publications

(2 citation statements)

References 16 publications

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“…The interaction between DNA adduct formation and cell proliferation has also been demonstrated utilizing different agents to produce the different events (18). N-[4-(5-nitro-2-furyl]-2-thiazoly]formamide (FANFT) is also genotoxic, leading to DNA adduct formation and mutagenic events in the bladder epithelium.…”

Section: Urinary Bladder Cancer Pathogenesismentioning

confidence: 99%

Urinary Bladder Carcinogenesis

Cohen

1998

Toxicol Pathol

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152

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Urinary bladder carcinogenesis in rodents bears numerous similarities to the diseases in humans. In rats, the process progresses through the morphologic stages of simple hyperplasia, papillary and nodular hyperplasia, papilloma, noninvasive, and invasive carcinoma. In mice, the pathogenesis can be similar or can follow a sequence of marked dysplasia with or without hyperplasia, leading to carcinoma in sirir and ultimately to high-grade invasive carcinoma. Although the papillary and nonpapillary diseases appear to be related in rodents and in humans, they are distinct morphologically, biologically, and molecularly. Numerous classes of genotoxic chemicals have been identified as bladder carcinogens in rodents, and some of these have also been identified as carcinogenic in humans, most notably, aromatic amines, nitrosamines, and cyclophosphamide. In contrast, nongenotoxic chemicals appear to be highly specific with respect to species, strain, diet, agent, dose, and mechanism. For some, it is unclear whether the results at high doses in rodents can be extrapolated to low doses or to humans, e.g., chemicals that cause bladder cancer only at high doses related to the formation of calculi. Numerous observations in rodents can assist in identifying possible mechanisms involved for these nongenotoxic chemicals and therefore can be important for a rational evaluation of human risk.Keycords. Bladder cancer; genotoxic chemicals; calculi; cell proliferation; hyperplasia URINARY BLADDER CANCER PATHOGENESIS Evidence increasingly is accumulating to support the hypothesis that transitional cell carcinoma of the urinary bladder actually represents 2 distinct, albeit related diseases (24, 44). The first type is papillary transitional cell carcinoma, which is usually low grade and noninvasive but tends to recur frequently following treatment. The second disease is the nonpapillary type that tends to be high grade and invasive, and it is frequently lethal to the patient due to local aggressiveness and/or distant metastases. In addition to differing pathogenetic processes, these 2 diseases appear to involve different molecular events (44). In animal models, these 2 diseases are similar to those in humans but tend to occur separately (9).In rats, bladder cancer is nearly always of the papillary type (9). The pathogenetic process for this disease involves the initial appearance of simple hyperplasia that may be diffuse or focal. This gradually evolves into focal areas of nodular and/or papillary hyperplasia, followed by evolution to a papilloma and ultimately to noninvasive low-grade carcinoma. In contrast to the disease in humans (9, 24), the papillary low-grade tumors eventually evolve into high-grade lesions and invasion, but they only rarely metastasize. Some other distinctions between the rat model and the human disease include the morphologic appearance of the papillomas, particularly the larger ones. In rats, these more closely resemble the inverted type of papilloma of humans rather the typical fronds of papillary trans...

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Section: Urinary Bladder Cancer Pathogenesismentioning

confidence: 99%

Urinary Bladder Carcinogenesis

Cohen

1998

Toxicol Pathol

Self Cite

152

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“…Metabolic processes in the bladder epithelium are similar in the rat and in the human. This has been most extensively examined for AAF in the mouse model, but similar considerations appear to be valid with respect to the rat Cohen and Ellwein 1995). This is particularly true in extrapolating qualitatively and quantitatively between the results for specific chemicals.…”

Section: Relevance To Human Diseasementioning

confidence: 87%

Urinary System

1998

Monographs on Pathology of Laboratory Animals

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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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Relationship of DNA Adducts Derived from 2-Acetylaminofluorene to Cell Proliferation and the Induction of Rodent Liver and Bladder Tumors

Cited by 21 publications

References 16 publications

Urinary Bladder Carcinogenesis

Urinary Bladder Carcinogenesis

Urinary System

Aromatic Nitro and Amino Compounds

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