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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoting effects of various chemicals on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats were given BBN at 0.01% or 0.05% in their drinking-water for four weeks. One of the following chemicals was then administered in the diet for 32 or 34 weeks: acetazolamide, allopurinol, phenobarbital, phenacetin, ortho-phenylphenol, sodium ortho-phenylphenate, diphenyl, sodium L-ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, sodium saccharin, aspartame, sodium cyclamate, stevioside, DL-tryptophan, quercetin, caffeine, nicotine and hippuric acid. Phenacetin, sodium ortho-phenylphenate, sodium L-ascorbate and butylated hydroxyanisole were significant promoters of urinary bladder neoplasia in rats initiated with BBN. Sodium saccharin, diphenyl, butylated hydroxytoluene, allopurinol, and DL-tryptophan caused moderate or slight promotion of neoplastic changes in the experimental animals. No change in tumour yield was observed after administration of the other chemicals.
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PMID:Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis. 653 4

Autoradiograms obtained 1-4 h after i.v. injection of the 14C-labelled carcinogenic tryptophan pyrolysis product Trp-P-1 to albino and pigmented mice showed a pronounced uptake of radioactivity in the lymphatic system (thymus, lymph nodes, bone marrow and spleen), in the endocrine system (hypophysis, thyroid, adrenal medulla) and in the liver, kidney medulla and brain. High radioactivity was present in the excretory pathways, predominantly in the bile/intestinal contents. At longer post-injection times (24 h to 6 days) most of the labelled substance had left the tissues, except for the liver which still retained a high concentration of radioactivity. Trp-P-1 is known to be activated by cytochrome P-448. The uptake of radioactivity in the liver could be reduced by pretreatment with the cytochrome P-448 inhibitor 9-hydroxyellipticine suggesting that the observed accumulation of radioactivity in the liver was partly due to metabolites of Trp-P-1. After pretreatment with the cytochrome P-448 inducer beta-naphthoflavone, the administration of Trp-P-1 resulted in a highly selective accumulation of radioactivity in the lung parenchyma, exceeding all other tissues in the body. beta-Naphthoflavone pretreatment also increased the uptake of radioactivity in the kidney cortex and small intestinal mucosa. As indicated by a high labelling of the pigmented tissues of the maternal and fetal eye, the carcinogen and/or its metabolites were accumulated in melanin.
Carcinogenesis 1983 Oct
PMID:Distribution of the carcinogenic tryptophan pyrolysis product Trp-P-1 in control, 9-hydroxyellipticine and beta-naphthoflavone pretreated mice. 661 57

We developed a short term assay for screening promoters of bladder cancer. This assay, in which maintenance of concanavalin A-agglutination of isolated rat bladder cells induced by subcarcinogenic treatment with bladder carcinogen is measured, suggested the possible promoting effects of L-isoleucine, L-leucine, D-tryptophan, and L-valin. Long term in vivo carcinogenesis experiments were carried out on L-isoleucine and L-leucine and it was shown that both were, in fact, promoters of bladder cancer in rats.
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PMID:L-Isoleucine and L-leucine are promoters of bladder cancer in rats. 668 Jul 28

We studied the capacity of various chemicals to promote urinary bladder cancer in male F344 rats after initiation by N-nitroso-n-butyl-(4-hydroxybutyl)amine (BBN). The rats were given initially 0.01% BBN in the drinking-water for 4 wk and then the test compound in the diet for 34 wk. Effects were judged by measuring the formation of preneoplastic lesions papillary or nodular hyperplasia (PN hyperplasia) of the urinary bladder. Administration of 5%, but not 0.5% (w/w) sodium saccharin in the diet significantly increased the incidence and extent of PN hyperplasia. This finding could be related to the induction of cancers in the rat urinary bladder by high levels of saccharin. Sodium ascorbate (5%). DL-tryptophan (5%) and allopurinol (0.02%) also significantly increased the extent of PN hyperplasia in the affected animals, but other test chemicals, such as acetazolamide (0.35%) and quercetin (5%) did not. The results with sodium saccharin and DL-tryptophan were consistent with previous findings and suggest that sodium ascorbate and allopurinol have promoting activities in urinary bladder carcinogenesis in rats. No correlation was found between the extent of crystalluria and promotion of preneoplastic lesions.
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PMID:Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N-nitroso-n-butyl-(4-hydroxybutyl)amine. 668 93

Male F344 rats were pretreated with various dietary compounds, and the effects of pretreatment on the in vitro alpha-hydroxylation of N-nitrosopyrrolidine or N'-nitrosonornicotine were determined in assays with liver microsomes or cultured esophagus, respectively. Dietary compounds included phenols, cinnamic acids, coumarins, indoles, and isothiocyanates. Pretreatments were carried out either by administering the compound by gavage 2 hr prior to sacrifice (acute protocol) or by adding the compound to the diet for 2 weeks (chronic protocol). Acute pretreatment with benzyl isothiocyanate, allyl isothiocyanate, phenethyl isothiocyanate, phenyl isocyanate, and benzyl thiocyanate but not sodium thiocyanate inhibited formation of alpha-hydroxylation products of both nitrosamines. When the chronic pretreatment protocol was used, only phenyl isothiocyanate and sodium thiocyanate inhibited formation of alpha-hydroxylation products of both nitrosamines. Pretreatments with butylated hydroxyanisole, p-methoxyphenol, or N-acetylcysteine had little, if any, effect on the alpha-hydroxylation of N-nitrosopyrrolidine or N'-nitrosonornicotine. Chronic pretreatment with p-hydroxycinnamic acid, 4-hydroxy-3- methoxycinnamic acid, coumarin, umbelliferone, limetine , indole, indole-3-carbinol, indole-3-acetonitrile, and L-tryptophan induced activity for the alpha-hydroxylation of N-nitrosopyrrolidine. The results of this study indicate that isothiocyanates are possible candidates for further study as potential inhibitors of carcinogenesis by N-nitrosopyrrolidine and N'-nitrosonornicotine.
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PMID:Effects of dietary compounds on alpha-hydroxylation of N-nitrosopyrrolidine and N'-nitrosonornicotine in rat target tissues. 672 18

Recent epidemiological surveys have indicated that alcoholics exhibit increased incidences of a variety of cancers. We have investigated, as a possible contributing factor to carcinogenesis in this population, the effect of chronic ethanol consumption on metabolic activation of procarcinogens by microsomes isolated from lungs and small intestine. These tissues are major sites through which procarcinogens enter the body and are also potential sites of procarcinogen metabolism. Rat litter-mates were pair-fed nutritionally adequate liquid diets which contained either ethanol as 36% of total energy or an equivalent energy content of carbohydrates in place of ethanol. Chronic ethanol consumption produced significant increases in pulmonary microsomal cytochrome P-450 and microsomal ethanol oxidation. The ethanol diet also enhanced the capacity of pulmonary microsomes to activate compounds present in tobacco pyrolyzates to mutagens detectable in the Ames Salmonella auxotroph reversion assay. The ethanol diet did not alter the capacity of pulmonary microsomes to hydroxylate benzo(a)pyrene (BaP) or to activate BaP to a mutagen. In contrast, microsomes from the upper small intestine of ethanol-fed rats did exhibit both higher levels of BaP hydroxylase activity and enhanced activation of BaP to a mutagen. The ethanol feeding also enhanced the capacity of the intestinal microsomes to activate to mutagens both tryptophan pyrolyzate and 2-aminofluorene but did not influence the metabolic activation of these promutagens by pulmonary microsomes. Chronic ethanol consumption thus influences carcinogen metabolism in the intestine and lung in a manner which varies with respect to both carcinogen and tissue.
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PMID:Enhanced pulmonary and intestinal activation of procarcinogens and mutagens after chronic ethanol consumption in the rat. 678 27

The co-carcinogenic activity of sodium saccharin and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was evaluated in male Fischer rats by co-administering them as 5% and 0.005% of the diet, respectively, for 2 years. The effect of simultaneous administration of two urinary bladder promoting substances, sodium saccharin and L-tryptophan as 5% and 2% of the diet, respectively, was also evaluated. Five of 16 rats administered sodium saccharin plus FANFT developed bladder tumors whereas none of the rats administered FANFT, sodium saccharin, or L-tryptophan alone, sodium saccharin plus L-tryptophan, or the control diet developed bladder tumors. Possible mechanisms for the co-carcinogenic activity of sodium saccharin and FANFT are discussed.
Carcinogenesis 1983
PMID:Co-carcinogenicity of sodium saccharin and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide for the urinary bladder. 682 91

The induction of cancer of the urinary bladder is a multi-stage process involving multiple exogenous and endogenous factors. Based on the classical initiation-promotion model, we have used N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as initiator and sodium saccharin (SAC) or tryptophan as promoters. These latter chemicals have the properties expected of promoters: induction of hyperplasia, reversibility and nonmutagenicity. Also, tumors were induced whether the promoter was administered immediately after FANFT or beginning 6 weeks after FANFT was discontinued, but no tumors resulted if either promoter was given without initiation with FANFT. Factor(s) present in normal urine also are involved in the promotion process, in addition to the role of urine as a carrier of carcinogens. However, administration of SAC to animals with a rapidly proliferating bladder mucosa, induced by ulceration, pellet insertion, or in utero, resulted in bladder tumor induction, even without prior initiation with FANFT. To better understand the complex interaction of the multiple variables in bladder carcinogenesis, a stochastic computer model has been formulated based on long-term carcinogenicity and tissue kinetic studies in vivo. This model indicates the importance of cell proliferation and the development of hyperplasia in carcinogenesis.
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PMID:Multistage carcinogenesis in the urinary bladder. 683 93

Adult rat hepatocytes in primary culture were used to study the effect of tryptophan pyrolysis products on the transcriptional process. Hepatocytes were treated with 1, 5 and 10 micrograms/ml of 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]-indole (Trp-P-1) or 3-amino-1-methyl-5H-pyrido-[4,3-b]-indole (Trp-P-2) for 2 and 4 h. The ultrastructural study revealed the appearance of nucleolar microsegregation accompanied by a reduction in peri- and interchromatin fibrils and granules in hepatocytes exposed to 10 micrograms/ml of each pyrolysate for 1 or 2 h. Biochemical investigation showed that the incorporation of [3H]uridine into nuclear RNA of treated hepatocytes was strongly decreased. Time- and concentration-related inhibition have been established; however, the inhibitory effect of Trp-P-1 was always superior to that of Trp-P-2. The determination of Mg2+-dependent RNA polymerase activity in an in vitro system functioning with isolated rat liver nuclei incubated in the presence of Trp-P-1 or Trp-P-2 showed a 40% inhibition of this activity. After a 1-h exposure of hepatocytes to 5 and 10 micrograms/ml of Trp-P-1, the recovery of RNA synthesis capacity was complete by 2 h and that of normal ultrastructural aspect was achieved within 4 h. All these results indicated that Trp-P-1 and Try-P-2 acted at the nucleolar level by a blockade of pre-rRNA synthesis and at the extranucleolar by decreasing the ultrastructural RNP responsible for hnRNA synthesis.
Carcinogenesis 1983
PMID:Ultrastructural and biochemical alterations induced by tryptophan pyrolysis products on rat hepatocytes in primary culture. I. Action on the transcriptional process. 683 20

Multistage models of carcinogenesis proposed to account for the observed patterns of tumor development in the skin, liver, lung, bladder and other organs involve initiation of neoplastic change in a few cells by a threshold dose of carcinogen followed by conversion of these latent tumor cells into an autonomous cancer by further doses of the same and/or other carcinogens, and/or noncarcinogenic promoting agents. In the rat urinary bladder, neoplastic change can be initiated by a few weeks treatment with low doses of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or by a single, low dose, intravesicular instillation of N-methyl-N-nitrosourea (MNU). Very few animals treated thus will develop bladder cancer unless exposed subsequently to some further regime which will promote tumor growth from the initiated cells. Many different factors will stimulate tumor growth in the initiated rat bladder, including further low doses of complete bladder carcinogens, dietary factors such as metabolites of tryptophan or deficiency of vitamin A, the food additives saccharin and cyclamate and some alkylating agents such as cyclophosphamide and methylmethane sulfonate. New and published evidence is reviewed which supports the belief that these and other factors are promoters or later stage carcinogens in the bladder. The difficulties of defining a promoter and of identifying markers of promotion, i.e., of distinguishing the second from the later stages of carcinogenesis in the urinary bladder, are discussed with reference to the action of promoters in the mouse skin initiation/promotion model. However, in terms of their effect on an initiated population on the risk of developing cancer, it is suggested that such a distinction is largely irrelevant. Since both second and later stage carcinogens accelerate tumor development in an initiated urothelium, they both have the potential to lower the age at which bladder cancer becomes symptomatic. They are thus as important as are initiating carcinogens in determining the patterns of age-related neoplastic disease in any population.
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PMID:Effect of promoters on incidence of bladder cancer in experimental animal models. 687 29


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