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

A modified Coffey I ureterosigmoidostomy has been developed in rats as a model of urinary diversion for studying bladder carcinogenesis and co-carcinogenesis. Diverted and sham-operated animals were killed at 1, 3 and 6 months. Excretory urograms revealed minimal hydroureteronephrosis in most diverted animals. Upper tract bacterial colonisation was 9 times more frequent in diverted animals. Approximately one-third of the diverted animals had focal cortical scarring; however, renal function was normal in all groups as assessed by serum creatinine and electrolytes. These studies indicate that ureterosigmoidostomy in rats is a satisfactory model of urinary diversion for studying carcinogenesis.
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PMID:Ureterosigmoidostomy in rats: a model for the study of bladder tumour carcinogenesis and cocarcinogenesis. 45 80

Epidemiologic studies have demonstrated an inverse relation between vitamin A intake and lung cancer rate. There is strong evidence that the provitamin A, beta-carotene, plays a more important role in the protective effect than vitamin A itself. The anticarcinogenic properties of beta-carotene have so far been attributed to its scavenger properties in deactivating or trapping reactive chemical species such as singlet oxygen and certain organic free radicals. Smoking results in increased excretion of detoxification products of electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic intermediates are involved in carcinogenesis, we performed a double-blind, placebo-controlled intervention trial to investigate whether the intake of beta-carotene by smokers would affect urinary thioether excretion. Before the intervention the beta-carotene group (n = 62) and the placebo group (n = 61) had similar thioether excretion levels in urine (4.2 vs 4.3 mmolSH/mol creatinine). During the intervention (20 mg beta-carotene daily for 14 weeks) the placebo group showed a 12% increase, whereas the beta-carotene group showed a 5% decrease (P = 0.004). After the intervention the beta-carotene group had a 15% lower thioether excretion level than the placebo group (4.1 vs 4.7 mmolSH/mol creatinine; P = 0.0017). Our study shows that urinary thioether excretion varies considerably over time, and that smokers have a decreased excretion of thioethers in urine after the use of beta-carotene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased excretion of thioethers in urine of smokers after the use of beta-carotene. 139 32

A mixture of 100 mM creatinine and 100 mM L-phenylalanine was heated at 60 or 37 degrees C in the presence of sugar or aldehyde. A mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formed in the model system was determined by reversed-phase HPLC. Any sugars tested induced the formation of PhIP when heated at 60 degrees C, though PhIP was not detected in a mixture without sugar. Among the sugars tested, D-erythrose and D-glyceraldehyde were more productive than pentose (D-arabinose and D-ribose) and hexose (D-glucose and D-galactose) in the yield of PhIP. Moreover, PhIP was formed even when a mixture of creatinine, L-phenylalanine and D-glucose or D-ribose was incubated at 37 degrees C for a long time. Both formaldehyde and acetaldehyde also induced the formation of PhIP, though PhIP was not detected in a mixture without sugar or aldehyde even when heated at 100 degrees C. These results indicate that PhIP can be formed at low-temperature heating and that either sugar or aldehyde is essential for PhIP formation in the model system. Our data also suggest that aldehydes may be a key reactant in the formation of PhIP in aqueous heating of the mixture of creatinine and L-phenylalanine.
Carcinogenesis 1992 May
PMID:Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating. 158 94

Recently it has been known that the active form of vitamin D, 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), plays some immunological roles in controlling cell differentiation and carcinogenesis. Moreover, 1 alpha, 25-(OH)2D is said to have some effects in the changes of several numbers of oncogenes. In this study, the serum concentrations of 1 alpha, 25(OH)2D and 25-hydroxyvitamin D (25-(OH)2D) were measured in 30 patients with renal cell carcinoma. The two vitamin D metabolites were separated and purified using high performance liquid chromatography, and each fraction was subjected to competitive protein binding assay using vitamin D deficient rat serum for 25-(OH)2D and chick embryo intestinal receptors for 1 alpha, 25-(OH)2D as the binder. The average concentration of serum 1 alpha, 25-(OH)2D was 28.9 +/- 5.2 pg/ml for controls whereas the average in patients with renal cell carcinoma was 19.7 +/- 5.9 pg/ml. The concentration of 1 alpha, 25-(OH)2D was significantly lower in the patients with renal cell carcinoma compared to in the controls (p less than 0.01). The average concentrations of serum 25-(OH)2D had no significant differences between the two groups. Comparison between the stage I + II and stage III + IV, T1 + T2 and T3 + T4, rapid type and slow type groups showed that the average serum 1 alpha, 25-(OH)2D concentrations was significantly lower in the stage III + IV, T3 + T4, and rapid type groups compared to the other groups (p less than 0.01, p less than 0.05, p less than 0.01). And besides there were no significant correlations between the concentration of serum 1 alpha, 25-(OH)2D and creatinine clearance in patients with renal cell carcinoma. Taken together, it is suggested that the serum concentration of 1 alpha, 25-(OH)2D is in some way correlated with the progression of renal cell carcinoma.
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PMID:[A study of the metabolism of vitamin D in patients with renal cell carcinoma--with special reference to serum concentration of 1 alpha, 25-(OH)2D and its clinical significance]. 188 Oct 8

Four monoclonal antibodies, PhIP-1, -2, -3 and -4, have been produced that bind to PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine), a mutagenic aromatic amine produced in meat by cooking. The immunogen was an analog of PhIP conjugated to a carrier protein through the 2-amino group of PhIP, leaving the pyridine and phenyl rings unmodified. The antibodies show a range of binding specificities for PhIP and its structural analogs, with PhIP-1 being the most highly selective, requiring the entire PhIP molecule with the exception of the exocylic amino group to be present for recognition. A competition enzyme linked immunosorbent assay (ELISA) incorporating these antibodies was developed and applied to the analysis of fried meat extracts differing in mutagen content. In extracts of fried beef, more PhIP-like material was found than would be expected based on chemical estimates of the amount of PhIP, suggesting that frying produces other compounds that are structurally similar to PhIP. These PhIP-like compounds were separated from PhIP using HPLC. Addition of creatinine to the beef prior to frying increased both the mutagenicity of the extracts and the amount of PhIP-like material. Microwave pre-treatment prior to frying reduced both immunochemical reactivity and mutagenicity.
Carcinogenesis 1989 Dec
PMID:Monoclonal antibodies to 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and their use in the analysis of well-done fried beef. 259 Oct 10

An in vivo model of liver hyperplastic noduligenesis was induced in rats by long-term administration of thioacetamide (TAM) (50 mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III) complex were administered at 14, 9 and 5 days before the end of TAM treatment. Plasma and urine were obtained from either TAM or Rh(III) complex or TAM plus Rh(III) complex treated rats to determine the interactions of both substances with the biochemical parameters related to liver function. The rise in alkaline phosphatase (ALP), leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT) and the unchanged activities in the aspartate and alanine aminotransferases (AST, ALT) in plasma of TAM-treated rats indicated that the disease induced by this substance can be considered as a chronic obstructive biliary disease with indices of cell proliferation and tumors. The increased concentration of bilirubin both in the plasma and urine of TAM-treated rats suggested liver cholestasis and hepatobiliary obstruction. The very low values of creatinine clearance indicated that there was some degree of kidney failure due to the effect of TAM. The increased concentration of ammonia both in plasma and urine were probably a consequence of the decreased flux in the urea cycle in the liver. The Rh(III) complex alone did not produce significant changes in the plasma enzyme activities. The only significant changes were found in the concentrations of uric acid and ammonia in the urine. When the Rh(III) complex was administered to TAM-treated rats, significant restoration of the following parameters were observed: plasma enzymatic activities, blood bilirubin and ammonia, uric acid and creatinine in the urine and the creatinine clearance. These results suggest that the altered liver function induced by TAM can be restored by Rh(III) complex. The mechanisms by which this complex acts to counteract the TAM-induced changes are not yet established.
Carcinogenesis 1987 Nov
PMID:Effect of a rhodium complex on alterations of hepatic function in thioacetamide-induced hyperplastic noduligenesis in rats. 288 38

In an inhalation study rats were exposed to different doses of benzene, ranging from 1 to 500 p.p.m. The urine was sampled during the inhalation period of 8 h and for 24 h after exposure. S-Phenylmercapturic acid (S-PMA) in the urine was determined by amino acid analysis. Phenol was measured by gas chromatography/mass spectrometry. In both cases the correlation between benzene uptake and the excretion of the urinary metabolites was significant at the level of P = 0.01. The same significant correlation (P = 0.01) was demonstrable after i.p. administration of benzene at doses between 0.7 and 140.0 microliters/kg body weight. In the case of two collectives of workers who were exposed to air concentrations of up to 0.15 p.p.m. for 8 h and of up to 1.13 p.p.m. for 12 h respectively, the amount of S-PMA in the first urine samples after the shift was significantly higher than in samples collected at the beginning of the shift (P = 0.01). In the first collective the mean values and the standard deviations of the S-PMA concentrations in the samples at the beginning of the shift were 12.0 +/- 16.7 compared with 48.5 +/- 64.5 micrograms/g creatinine at shift end. In the second collective they were 25.1 +/- 25.1 compared with 70.9 +/- 109.2 micrograms/g creatinine. The level of significance of the difference between the concentration values of S-PMA at the beginning and end of the shift was P = 0.01. The phenol concentration did not differ significantly. These results suggest that S-PMA can be regarded as a useful indicator for monitoring individuals and collectives exposed to benzene at levels even less than 1 p.p.m.
Carcinogenesis 1989 Feb
PMID:Determination of S-phenylmercapturic acid in the urine--an improvement in the biological monitoring of benzene exposure. 291 79

Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N-nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances.
Carcinogenesis 1989 Mar
PMID:Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer. 292 2

We investigated the possibility that variations of the metabolism of xenobiotic compounds might be involved in the process of bladder carcinogenesis, by studying activation reactions (phase I) and detoxification reactions (phase II) of xenobiotic compounds in a group of patients with transitional cell carcinoma of the bladder and in a group of controls hospitalised with other diseases. As an indirect estimate of activating reactions (phase I) we measured cortisol hydroxylation, expressed as the ratio between urinary 6-beta-OH-cortisol and 17-OH-corticosteroids. Cortisol hydroxylation was not increased in the group of patients when compared with controls. The variations of phase II conjugating enzymes were followed indirectly by administering paracetamol and measuring the urinary excretion of its main metabolites over a period of 12 h. The variations in the metabolic conjugation of paracetamol were expressed as a percentage of each metabolite, or of unmodified paracetamol excreted in the urine, or as the ratio between a given metabolite and unmodified paracetamol. The data were analyzed with a logistic regression model, analysing the effects of possible confounding variables such as age, smoking, alcohol, blood nitrogen, blood creatinine, glutamic-pyruvic (SGPT), glutamic-oxalacetic transaminases (SGOT) and percent recovery of paracetamol in the urine. Statistical analysis showed that the excretion of mercapturate derivatives of paracetamol was significantly increased in the group of patients. The levels of glucuronic, sulphate and cysteine metabolites were not varied significantly. Since mercapturate derivatives are formed as a consequence of the formation of short-lived metabolites of paracetamol which react with protein, nucleic acids or glutathione, the increased excretion of mercapturic acid derivatives in cancer patients might be an indication of a higher capability of forming reactive molecular species from xenobiotic compounds. We suggest that this factor might play a role in the induction of bladder cancer.
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PMID:Variations of cortisol hydroxylation and paracetamol metabolism in patients with bladder carcinoma. 320 22

Urine mutagenicity of 19 individuals was investigated at a steel mill. All the subjects worked on the coal processing unit. Urine samples were collected at the end of a working day. Urine samples of two exposed workers were collected at the end of two periods of rest and two periods of working. Mutagens were extracted on XAD-2 resin and tested by the Salmonella microsomal assay and the SOS spot test. Mutagenic potencies of exposed smokers and exposed non-smokers were 8.62 +/- 6.56 and 1.1 +/- 0.48 revertants/mg creatinine respectively with Salmonella typhimurium strain TA98 + S9. Both values were significantly higher than those of unexposed smokers and non-smokers (5.07 +/- 3.33 and 0.47 +/- 0.72 revertants/mg creatinine respectively). The urinary mutagenic potency of the two exposed individuals increased at the end of periods of working (15.97 +/- 2.57 revertants/mg creatinine) and decreased at the end of periods of rest (12.31 +/- 2.45 revertants/mg creatinine). Urinary mutagens were detected with S. typhimurium strain TA100 + S9 to a lesser extent. No direct-acting mutagens were detected by the SOS spot test. Atmospheric benzo[a]pyrene (BaP) were also measured by h.p.l.c. on the coke battery. BaP concentrations ranged between 0.01 and 0.6 microgram/m3 air at the different working sites. Biological monitoring with short-term tests is discussed.
Carcinogenesis 1987 Mar
PMID:Urine mutagenicity of steel workers exposed to coke oven emissions. 354 25


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