Effects of Promoters on N-Butyl-N-(4-hydroxybutyl)nitrosamine-Induced Urinary Bladder Carcinogenesis in the Rat

Abstract

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives.It has been shown that the occurrence of the preneoplastic lesion, papillary or nodular hyperplasia (PN hyperplasia) in rat urinary bladder induced by carcinogens is correlated with that of cancer. Therefore, the promoting effects of chemicals in two-stage bladder carcinogenesis were judged by measuring their ability to induce PN hyperplasia in rats. Male rats were given N-butyl-N44-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then one of 16 test chemicals for 32 to 34 weeks. Saccharin, ascorbate, DL-tryptophan, allopurinol, and diphenyl promoted development of PN hyperplasia. The dose-response of the promoters were examined in both sexes of rats by administration of saccharin at doses of 0.04, 0.2, 1.0 and 5.0% for 32 weeks after BBN treatment. The occurrence of PN hyperplasia was significantly increased in the group given 5% saccharin. Dose-response curves showed enhanced hyperplastic responses in both sexes given 0.2 to 5% saccharin.The organ specificities of promoters were studied in rats initiated with BBN or 2-acetylaminofluorene (2-AAF) followed by phenobarbital or saccharin for 32 weeks. Phenobarbital greatly enhanced hepatocarcinogenesis. Saccharin significantly enhanced the occurrence of both BBN-induced and 2-AAF-induced PN hyperplasia. However, there was no effect of phenobarbital on the urinary bladder or of saccharin on the liver.The rats showed a strain difference in susceptibility of the urinary bladder to saccharin; ACI rats were most susceptible and Sprague Dawley rats were most resistant to saccharin.The membrane potential of superficial epithelial cells in the urinary bladder of rats treated with saccharin was measured with an intracellular microelectrode and found to be higher than that of controls.

Carbonic anhydrase 2 is a novel invasion‐associated factor in urinary bladder cancers

“…In the present study, we established a new 16‐week rat invasive bladder cancer model using Hras128 rats treated with BBN followed by PEITC. Chemically‐induced rat urinary bladder cancer in the existing models is nearly always non‐invasive UC that closely resembles the pathologic characteristics of its human counterpart, non‐invasive pTa tumors . The advantages of our model are that it mimics invasive UC that arises from non‐invasive UC and the short period of time required for inducing invasive UC.…”

“…Chemically-induced rat urinary bladder cancer in the existing models is nearly always noninvasive UC that closely resembles the pathologic characteristics of its human counterpart, non-invasive pTa tumors. (15)(16)(17)(18)32,33) The advantages of our model are that it mimics invasive UC that arises from non-invasive UC and the short period of time required for inducing invasive UC. Our model is useful in understanding mechanisms by which non-invasive UC progresses to invasive UC; using this model, we identified 49 proteins differentially expressed in invasive rat UC by comparing invasive and non-invasive UC.…”

“…Chemically‐induced rat urinary bladder cancer is nearly always non‐invasive UC that closely resembles the pathologic characteristics of its human counterpart, non‐invasive pTa tumors . In the present study, we aim to establish a novel medium‐term chemically‐induced invasion model mimicking the invasive UC that arise from non‐invasive UC and to use this model to identify invasion‐associated factors.…”

“…Therefore, identification of invasion-associated factors during the process of acquiring invasive capability by pTa and pT1 tumors may provide new therapeutic strategies, improving the outcomes of UC patients.Chemically-induced rat urinary bladder cancer is nearly always non-invasive UC that closely resembles the pathologic characteristics of its human counterpart, non-invasive pTa tumors. (15)(16)(17)(18) In the present study, we aim to establish a novel medium-term chemically-induced invasion model mimicking the invasive UC that arise from non-invasive UC and to use this model to identify invasion-associated factors. The BBN-induced rat bladder cancer model is a widely used orthotropic model of human UC with short-term treatment of BBN being capable of inducing high incidences of non-invasive UC, (18,19) and Hras128 rats exhibit high susceptibility to…”

“…Chemically-induced rat urinary bladder cancer is nearly always non-invasive UC that closely resembles the pathologic characteristics of its human counterpart, non-invasive pTa tumors. (15)(16)(17)(18) In the present study, we aim to establish a novel medium-term chemically-induced invasion model mimicking the invasive UC that arise from non-invasive UC and to use this model to identify invasion-associated factors. The BBN-induced rat bladder cancer model is a widely used orthotropic model of human UC with short-term treatment of BBN being capable of inducing high incidences of non-invasive UC, (18,19) and Hras128 rats exhibit high susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis; (20,21) however, unlike other rat models, Hras128 rats treated with BBN also develop invasive UC.…”