Promotion in Urinary Bladder Carcinogenesis

Cohen, Samuel M.

doi:10.2307/3429534

Cited by 10 publications

(17 citation statements)

References 5 publications

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“…Tryptophan metabolites have also been regarded as promoter in carcinogenesis in the initiator-promoter model [Cohen, 1983]. Bryan and Springberg [1966] demonstrated that the administration of the 8-methyl ether of XA administered in a cholesterol pellet significantly increased the incidence of bladder tumors compared to the cholesterol pellet alone.…”

Section: Tryptophan or Its Metabolites As Promotersmentioning

confidence: 99%

Possible roles of excess tryptophan metabolites in cancer

Chung

Gadupudi

2011

Environ and Mol Mutagen

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Tryptophan is metabolized through serotonin, indole, and kynurenine (KN) pathways. Uptake of an excess amount of tryptophan accompanied with vitamin B6 deficiency may result in the accumulation of higher concentrations of metabolites mainly from the KN pathways in the bladder. These metabolites could interact with nitrite to become mutagenic nitrosamines. They could be a promoter in the initiator-promoter model of carcinogenesis. They produced bladder cancer when implanted in the bladder. They also interact with transition metals copper or iron to form reactive radicals or reactive oxygen species (ROS). Some metabolites, 3-hydroxy-anthranilic acid, were autooxidized to mutagenic cinnabarinic and anthranilyl radical intermediates. These radical intermediates could also be ligands that interact with aryl hydrocarbon receptor (AhR) and induce xenobiotic metabolizing enzymes (XMEs) to metabolize contaminated carcinogens. When tryptophan is exposed to either visible or UV light, a photoproduct of 6-formylindolo[3,2b]-carbazole is formed, which has a very high affinity for the AhR that plays a role in carcinogenesis. This review gives an insight into various mechanisms through which tryptophan metabolites cause carcinogenesis. It could be concluded that tryptophan metabolites play a complementary role in promoting carcinogenesis along with carcinogens like aflatoxin, CCl(4) , 2-acetylaminofluorene, 4-aminobiphenyl, 2-naphthylamine, or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide. The underlying mechanisms could be their autoxidation, exposure to either visible or UV light, interaction with nitrite or transition metals to form reactive intermediates, serving as ligands to interact with an AhR that is known to play a role in carcinogenesis through induction of XMEs. Further research is warranted.Environ.

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Section: Tryptophan or Its Metabolites As Promotersmentioning

confidence: 99%

Possible roles of excess tryptophan metabolites in cancer

Chung

Gadupudi

2011

Environ and Mol Mutagen

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“…Extensive experimental efforts have successfully identified several bladder specific carcinogens in rodent species (9,10,50,53). A continuum of stages in urinary bladder carcinogenesis has been established.…”

Section: Discussionmentioning

confidence: 99%

“…Neoplastic processes typically begin with simple hyperplasia, progress to papillary or nodular (PN) hyperplasia, and sometimes papilloma and invasive carcinomas. The model of initiation-promotion is also relevant to urinary bladder carcinogenesis (10). Observations of experimental urinary bladder carcinogenesis have suggested that 2 types of simple hyperplasia may exist, one reversible and the other nonreversible (20,50).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of urothelial hyperplasia and neoplasms of the rat urinary bladder is unusual in control animals (10). Extensive experimental efforts have successfully identified several bladder specific carcinogens in rodent species (9,10,50,53).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of cell proliferation and changes at the DNA level in a target organ are considered essential for initiation and cancer development (6). Sequential administration of single urinary bladder carcinogens, followed by other complete or incomplete carcinogens, has been shown to result in an increase in urinary bladder tumor incidence compared to carcinogens administered alone (10,51).…”

Section: Discussionmentioning

confidence: 99%

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Induction of Transitional Cell Hyperplasia in the Urinary Bladder and Aberrant Crypt Foci in the Colon of Rats Treated with Individual and a Mixture of Drinking Water Disinfection By-Products

et al. 2003

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Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of chlorinated surface water containing disinfection by-products (DBPs). The present study was designed to determine if exposure to DBPs would cause preneoplastic or neoplastic lesions in the urinary bladder and colon of rats, and what effect a mixture of DBPs would have on these lesions. Male and female Eker rats were treated via drinking water with low and high concentrations of potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H )-furanone (MX), chloroform, or bromodichloromethane individually or in a mixture for 10 months. The urinary bladders and colons were examined for the presence of preneoplastic lesions. Cell proliferation in the urothelium was examined using immunohistochemical staining for bromodeoxyuridine. Aberrant crypt foci (ACF), as well as the number of individual crypts in each ACF, were identified and counted microscopically after staining with 0.2% methylene blue. Colon crypt cell proliferation and mitotic index were determined using immunohistochemical staining for proliferating cell nuclear antigen. Labeling indexes for the urinary bladder and colon were calculated based on the percentage of positively labeled cells. Treatment with the high dose of MX caused transitional epithelial hyperplasia and cell proliferation in the rat urinary bladder, and this effect was diminished in the high dose mixture animals. Treatment with 4 individual DBPs, as well as a mixture of them, caused the development of ACF, the putative preneoplastic lesion of colon cancer.

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Mutations and expression of the p53 gene in rat bladder carcinomas and cell lines

Asamoto¹,

Mann²,

Macatee³

et al. 1994

Molecular Carcinogenesis

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Abnormalities of the p53 gene are frequently observed in human tumors, including urinary bladder carcinoma, suggesting that p53 plays an important role in human carcinogenesis. However, its role in rat bladder carcinogenesis is unclear. We investigated p53 gene mutations and expression in rat urinary bladder carcinogenesis in vivo and in vitro. Fifteen urothelial cell lines, including six untransformed (nontumorigenic) ones, six transformed (tumorigenic) in vitro, and three derived from tumors induced in vivo, were examined for p53 expression by immunochemical analysis and for p53 mutations; in addition, 81 rat bladders were analyzed immunohistochemically for p53 expression, and 23 rat bladder tumors were analyzed for p53 mutations. Four cell lines had mutations in the p53 gene. Two of these were missense point mutations, and the other two were splicing mutations. On the other hand, no mutations were found in the bladder tumors induced in rats. By immunoprecipitation with PAb240, which is supposed to be specific for mutant p53, we detected mutations in three of the cell lines; PAb240 did not react with wild-type p53. However, in all cell lines and in growing populations of primary cultured bladder urothelial cells, p53 expression was detected immunohistochemically or by western blotting using PAb240 or PAb 421 monoclonal antibodies. In a high percentage of transitional cell carcinomas, wild-type p53 expression was detected by immunohistochemical analysis with PAb240. These results suggest that p53 gene mutations may not occur frequently in rat bladder carcinogenesis in vivo but may occur in vitro and that p53 overexpression detected immunohistochemically is common and may be related to cell proliferation rather than to the presence of mutations in rat bladder carcinogenesis.

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Promotion in Urinary Bladder Carcinogenesis

Cited by 10 publications

References 5 publications

Possible roles of excess tryptophan metabolites in cancer

Possible roles of excess tryptophan metabolites in cancer

Induction of Transitional Cell Hyperplasia in the Urinary Bladder and Aberrant Crypt Foci in the Colon of Rats Treated with Individual and a Mixture of Drinking Water Disinfection By-Products

Mutations and expression of the p53 gene in rat bladder carcinomas and cell lines

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