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

Pyrolysis products of proteins and amino acids are highly mutagenic, but metabolism of these chemicals by rat liver subcellular fractions is known to be required for production of the mutagenic intermediates. We examined the mutagenesis of seven purified pyrolysis products from tryptophan, lysine, glutamic acid, and soybean globulin with Salmonella typhimurium strain TA98 in the presence of liver fractions from genetically "responsive" C57BL/6N and Ah(b)/Ah(d) or "nonresponsive" DBA/2N and Ah(d)/Ah(d) mice that had been pretreated in vivo with benzo[a]pyrene. For all pyrolysis products tested, mutagenesis is 2-fold to more than 1000-fold greater with C57BL/6N and Ah(b)/Ah(d) than with DBA/2N or Ah(d)/Ah(d) liver fractions. A sucrose density gradient assay for detecting the Ah regulatory gene product, the receptor, was studied with C57BL/6N hepatic cytosol. At levels 100 times in excess of [1,6-(3)H]2,3,7,8-tetrachlorodibenzo-p-dioxin, nonlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, and beta-naphthoflavone (inducers of cytochrome P(1)-450) are able to displace the radioligand from its hepatic cytosolic receptor; four pyrolysates from tryptophan, glutamic acid, and soybean globulin did not have this capacity. These data indicate that the pyrolysis products tested, although not effective as inducers of cytochrome P(1)-450, are most mutagenic when metabolized by P(1)-450. Potent P(1)-450 inducers-present in pyrolysates during the combustion process-might be present in quantities insufficient to initiate mutagenesis or carcinogenesis but might have a synergistic action, or act as "comutagens" or "cocarcinogens," with the N-containing heterocyclic pyrolysis products. A quantitative relationship between mutagenic and carcinogenic potency of these pyrolysis products remains, however, to be demonstrated.
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PMID:Pyrolysis products from amino acids and protein: highest mutagenicity requires cytochrome P1-450. 29 93

The existence of at least two stages in bladder carcinogenesis was evaluated in male Fischer rats using N-[14-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed for six weeks at a level of 0.2% of the diet as the initiator. Sodium saccharin and DL-tryptophan were fed at levels of 5 and 2% of the diet, respectively, as possible promoting chemicals, and they were fed either immediately after FANFT administration or after six weeks of FANFT plus six weeks of control diet. All surviving rats were killed at the end of two years. Both chemicals significantly increased the incidence of bladder tumors following FANFT feeding compared to six weeks of FANFT feeding followed by control diet, and the results were similar whether saccharin or tryptophan feeding was started immediately after FANFT feeding was concluded or after a six-week delay. Saccharin was considerably more potent as a promoting agent than was tryptophan, inducing higher incidences of bladder tumors and having a shorter latent period. Long-term administration of FANFT induced a 100% incidence of bladder cancer. Sequential epithelial changes were observed by scanning and transmission electron microscopy as well as by light microscopy. Pleomorphic microvilli were present on the superficial cells of all tumors examined and on the surface cells of hyperplastic bladder epithelium after six weeks of FANFT plus six weeks of saccharin, but not after six weeks of FANFT and six weeks of control diet. Rats fed only saccharin tryptophan, or control diet did not have bladder tumors or pleomorphic microvilli on bladder epithelium. These data suggest that saccharin and tryptophan might act as tumor-promoting agents during bladder carcinogenesis.
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PMID:Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis. 42 Dec 4

Urinary excretion before and after a loading dose of tryptophan, plasma pyridoxal phosphate concentration and urinary excretion of 4-pyridoxic acid was studied in 44 male bladder cancer patients from Copenhagen. Six patients (14%) had abnormal tryptophan metabolism, decreased plasma pyridoxal phosphate concentration and in most cases low urinary excretion of 4-pyridoxic acid indicating decreased availability of vitamin B6 or decreased formation of pyridoxal phosphate from vitamin B6. It is concluded that abnormal tryptophan metabolism only plays a minor role for bladder cancer carcinogenesis in Copenhagen. It is, however, stressed that such studies do not rule out the possibility that the aromatic degradation products of tryptophan may be cocarcinogens or promotors as other studies have indicated.
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PMID:Tryptophan metabolism in bladder cancer patients from Copenhagen. 48 65

In comparison with healthy age- and sex-comparable subjects, a significantly higher concentration of unconjugated 3-hydroxyanthranilic acid was detected in the urine of untreated bladder and kidney carcinoma patients. Because of tryptophan metabolite 3-hydroxyanthranilic acid is suspected to be involved in the carcinogenesis of bladder tumours, it is of importance to know if the concentration will normalize to the level of the control group after curation of the tumours, indicating that the aberration was a result of the disease itself. The first results from a study in bladder carcinoma patients during the follow-up after curation of the tumours suggest a persistent increase in the urinary concentration of free 3-hydroxyanthranilic acid.
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PMID:The excretion of 3-hydroxyanthranilic acid in patients with bladder and kidney carcinoma. 124 78

A total of 45 chemicals, including two aromatic hydrocarbons, five aromatic amines, three azo dyes, ten nitroso compounds, three steroids, four tryptophan metabolites and their related compounds, four naturally occurring substances, four pyrolysates of amino acids and ten miscellaneous compounds, were tested for newborn mouse tumorigenesis assay (NMTA). The results of the NMTA were compared with data from 'Survey of Compounds Which Have Been Tested for Carcinogenic Activity', NIH, NCI, USA (SCWHBTCA), and also with data from the IARC Monographs (Vols 1-41), Lyon, France (IARC). Of the 45 chemicals tested by the NMTA, 28 chemicals showed positive results in the NMTA, and the remaining 17 chemicals were found to be negative for tumor development. The correlation of the results between the NMTA and the mouse and/or rat carcinogenesis test starting at young adult age reported in the SCWHBTCA and in the IARC were compared with 37 chemicals tested; the remaining eight chemicals were found only in our NMTA results. It can be concluded that 31 out of 37 chemicals (83.8%) tested by the NMTA showed similar carcinogenic or non-carcinogenic results obtained in either adult mouse and/or rat carcinogenesis tests. The remaining six chemicals showed contradictory results between the NMTA and either adult mouse and/or rat carcinogenesis tests. Those six chemicals were N-hydroxy-4-acetylaminobiphenyl, estradiol, 3-hydroxyanthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. Among the 37 chemicals, 34 were comparable with the results of the adult mouse carcinogenesis test and those of the NMTA. Twenty-nine out of 34 chemicals (85.3%) showed similar results to the adult mouse carcinogenesis test. Contradictory results were obtained with the following five chemicals: N-hydroxy-acetylaminobiphenyl, 3-hydroxy-anthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. There were 35 chemicals which were comparable with the results of the adult rat carcinogenesis test, and 32 chemicals showed the same results as the NMTA (91.4%). Dissimilar results were obtained with the following three chemicals: estradiol, 3-hydroxy-anthranilic acid and phenobarbital. Based on the results presented in this report, it is reasonable to conclude that the NMTA is one of the most useful and reliable methods for detecting tumorigenic or non-tumorigenic chemicals, when a small amount of chemical is available for rodent carcinogenesis test and the duration of the study is limited to 1 year.
Carcinogenesis 1991 Aug
PMID:Evaluation of the newborn mouse model for chemical tumorigenesis. 186 Jan 62

A derivative of ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), is a strong scavenger of active oxygen species. We examined the effect of CV-3611 on a short-term test of bladder carcinogenesis, using concanavalin A (Con A)-dependent agglutination of isolated bladder epithelial cells. Rats were given 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for 1 week, and then 5% sodium saccharin or 2% DL-tryptophan or 0.01% BHBN alone or with 0.002, 0.006 or 0.02% CV-3611 for 3 weeks. Treatment with CV-3611 reduced the effects of the bladder tumor promoters sodium saccharin and DL-tryptophan by 48-86 and 65-87%, respectively. CV-3611 also reduced the number of aggregates of bladder epithelial cells from rats treated with BHBN for 4 weeks. These results suggest that CV-3611 has a suppressive effect on rat bladder carcinogenesis.
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PMID:Inhibitory effect of 2-O-octadecylascorbic acid in agglutination assay with concanavalin A; short-term examination of rat urinary bladder carcinogenesis. 190 18

We have shown that the urinary bladder secretes and binds to its surface a glycosaminoglycan layer whose nonspecific antiadherence effect protects the bladder from infection and perhaps from stone formation. If bladder cancer is caused by agents present in the urine, as is widely believed, this mechanism may also protect against carcinogenesis. We performed the current study to determine whether suspected carcinogens or cocarcinogens in the urine gain access to the transitional cells by impairing or inactivating the surface antiadherence effect. Using an in vivo method to quantitate bacterial adherence to the rabbit bladder, we compared adherence in control and glycosaminoglycan-deficient bladders to adherence in bladders treated with one of several suspected urinary carcinogens. There were statistically significant differences between adherence in control bladders and adherence in bladders treated with the tryptophan metabolites 3-hydroxykynurenine and 3-hydroxyanthranilic acid, sodium cyclamate, and sodium saccharin. These data indicate that perhaps certain suspected urinary bladder carcinogens inactivate the anti-adherence effect of the glycosaminoglycan layer at the bladder surface and thereby penetrate to the transitional cells to exert their tumorigenic effects; or they may serve as cocarcinogens that inactivate the glycosaminoglycan barrier and permit other urinary carcinogens to transform the transitional cells.
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PMID:Inactivation of antiadherence effect of bladder surface glycosaminoglycans as possible mechanism for carcinogenesis. 244 74

Solutions of several promutagens or of non-genotoxic carcinogens were exposed to sunlight or to artificial sources of UV or fluorescent light, under various experimental conditions. Irradiation resulted in the oxygen-mediated formation of direct-acting mutagenic and DNA-damaging photoproducts in bacteria, with evident structure-activity relationship. Of the aromatic amines tested, 2-aminofluorene and, with lower efficiency, 2-acetylaminofluorene were photoactivated, whereas irradiation of 4-acetylaminofluorene and of the 1- and 2-amino substitutes of anthracene and naphthalene did not produce mutagenic derivatives in Salmonella typhimurium. Of the heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline were extraordinarily sensitive to activation by sunlight and fluorescent light, which contrasted with the insensitivity of the tryptophan pyrolysis products. Use of optical and interference filters showed that near-UV light is the main component of solar radiation responsible for the formation of highly stable mutagenic derivatives. The mutagenicity of 2-aminofluorene and of the aminoimidazoquinoline compounds, following both metabolic and light activation, was lost in nitroreductase- and O-acetyltransferase-dificient bacteria. Benzo[alpha]pyrene was better activated by 254- than by 365-nm UV light. Sunlight did not affect the lack of mutagenicity of carcinogenic organochlorine pesticides, but exposure to 254-nm UV light selectively resulted in the formation of weak mutagens from dieldrin and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, but not from 4,4'-dichlorodiphenyltrichloroethane, lacking carbon-carbon double bonds.
Carcinogenesis 1989 Jun
PMID:Photoactivation of mutagens. 265 63

A simple and efficient method for the purification of mutagenic heterocyclic amines from heated meat products has been developed. In only two steps, namely extraction of raw material on Kieselgur followed by medium pressure liquid chromatography on Sephasorb HP, very clean fractions with high recovery rates of mutagenic compounds were obtained, thus allowing isolation and quantitation by high performance liquid chromatography (HPLC) with UV detection. The method was validated on both food grade and bacterial beef extracts as well as fried beef. In 1-5 g samples of beef extracts, levels up to 70 p.p.b. (ng/g) of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 8-90 p.p.b. of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and up to 8 p.p.b. of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were determined. In fried beef, 1 p.p.b. of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1 p.p.b. of MeIQx were measured. The quantitative results of beef samples were in agreement with results from determinations using immunoaffinity chromatography/HPLC or liquid chromatography coupled with mass spectrometry. MeIQx could be quantified in fried beef down to 1 ng/g of fresh beef material. According to assays performed with reference standards of tryptophan and glutamic acid pyrolysis products, the method could also be extended to quantitate other heterocyclic amines.
Carcinogenesis 1989 Jul
PMID:An efficient and convenient method for the purification of mutagenic heterocyclic amines in heated meat products. 266 Oct 43

Rutaecarpine alkaloids have the capacity to inhibit specific 2,3,7,8-[1,6-3H]tetrachlorodibenzo-p-dioxin (TCDD) binding in rat liver cytosol, as analysed by electrofocusing in polyacrylamide gel. The IC50 value for binding of 7,8-dehydrorutaecarpine was estimated to approximately 7 nM indicating a high-affinity interaction, whereas rutaecarpine appeared less active (IC50 approximately 110 nM). These findings are of interest in view of the fact that analogues to these compounds may be formed following UV-irradiation of tryptophan and that such photo-products have been suggested to constitute (the) endogenous ligand(s) for the TCDD receptor. As further support of this notion, the rutaecarpine alkaloids investigated could be fitted into a rectangle of 6.8 x 13.7 A, a characteristic common for most high affinity ligands of the TCDD receptor hitherto studied. In view of their structural similarity to dehydrorutaecarpine and the agreement of their mol. wt with that of the photoproduct with the highest affinity for the TCDD receptor, we suggest deaza-analogues of dehydrorutaecarpine to represent possible candidates for the endogenous TCDD receptor ligand.
Carcinogenesis 1989 Apr
PMID:Interactions of rutaecarpine alkaloids with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. 270 13


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