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

Gastric cancer is the world's overall second most common cancer, and carries a bad prognosis. In the Correa model of gastric carcinogenesis, environmental factors (salt, nitrate, a lack of vitamin C and beta-carotene, bile reflux, bacterial overgrowth in atrophic gastritis with nitrosamine formation) are related to the evolution from normal gastric tissue through superficial gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to carcinoma. The incidence of H. pylori decreases with progressing preneoplastic lesions. In several studies, the prevalence of H. pylori was elevated in patients with gastric cancer, with a trend for a higher prevalence in intestinal type gastric cancer vs diffuse type. Family members of patients with gastric adenocarcinoma have a higher H. pylori prevalence than controls; patients infected with H. pylori have more family members with gastric cancer. Several epidemiological studies showed a higher H. pylori prevalence in regions or populations with high gastric cancer risk vs low-risk populations. Large-scale studies in China and Europe showed a correlation between H. pylori seroprevalence and gastric cancer incidence and mortality. Three prospective nested case-control studies showed that infection with H. pylori increased the risk of further development of gastric adenocarcinoma, showing that H. pylori infection precedes the development of gastric cancer. Several pathways can be identified explaining the association between H. pylori and gastric adenocarcinoma. We showed that gastric cell proliferation is increased in parallel with inflammation. The ascorbic acid concentrating mechanism is abolished in gastritis. Ammonia, generated by H. pylori's urease, gives rise to gastric mucosal atrophy. We showed that salt increases the gastric cell proliferation only in H. pylori-infected individuals. The organism's toxin may play a role in gastric cancer. Besides H. pylori, other environmental factors are important in determining the gastric cancer risk. For instance, we showed that in Belgium, Maghreb immigrants have a high prevalence of H. pylori infection but a low prevalence of intestinal metaplasia and gastric cancer. Gastric lymphoma is rare (about 5% of all gastric tumours), but its incidence is steadily increasing. It was shown that H. pylori also increases the risk for low-grade as well as high-grade gastric lymphoma. Eradication of H. pylori has been shown to cure several cases of unequivocally proven gastric low-grade lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Helicobacter pylori: the link with gastric cancer. 806 90

The incidence of cervical cancer is known to decrease with the Westernization of life style. The purpose of this study was to see whether or not the practice of pseudopregnancy conditioning (psp-c) and/or non-Western (rice-rich or rice-and salt-rich) diet conditioning (dt-c) in female mice can reproduce a specific steroidal disorder that is associated with cervical cancer--general depression of androgen and partial depression of corticoid in urine. The effects of psp-c and dt-c were assessed by estimating various steroids in urine and plasma of mice, as collected at the terminal stage of the experiment. Macroscopic and microscopic changes of genital organs were also investigated by dissection. Results obtained are as follows: 1) the practice of psp-c and/or dt-c induced a total of 13 deciduomas in the vagina, the cervix and the corpus of experimental mice. No deciduoma was found in virgin mice fed a standard (Western-style) diet. 2) The combination of 2 reproductive markers (psp-c and non-psp-c) and 3 dietary markers (standard diet, rice-rich diet and rice- and salt-rich diet) produced a variety of changes in the excretions of all androgens, progestins and corticoids in the urine of mice for each of 5 experimental groups. A common steroidal trait was extracted from the urinary steroid data of 5 experimental groups--general depression of androgens, progestins and majority corticoids relative to tetrahydrocortisol. By the collation test, the combination of psp-c and rice- and salt-rich diet conditioning was found to be the best choice for reproducing the urinary steroid changes specific for cervical cancer. 3) The results of plasma steroid analysis, though not incompatible with the urinary steroid data, were fragmentary and not very informative in this study. The observed resistance of mice to carcinogenic insults together with the possible role of deciduoma in cervical carcinogenesis is discussed in the light of relevant information including the anti-carcinogenic action of vitamin C.
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PMID:Hormonal implication of diet and reproductive activity in the genesis of cervical cancer. 807 49

Using an initiation-promotion rat model, we have previously shown that the alkalizing salt KHCO3 is a strong and the neutral salt KCl a weak promoter of urinary bladder carcinogenesis. We have now studied the effects of these salts on rat urinary bladder epithelium without prior exposure to a bladder tumour initiator. In four studies ranging in duration from 4 to 130 weeks, (equimolar) amounts of K+ were administered in the diet to male and female rats (85 rats/sex/group) as KHCO3 or KCl. Comparable increases in urinary volume and potassium levels were found with both KHCO3 and KCl, but only KHCO3 induced an elevated urinary pH. The feeding of KHCO3 resulted in simple epithelial hyperplasia and, after prolonged administration, in papillary/nodular hyperplasia, papillomas and transitional cell carcinomas of the urinary bladder. With KCl, only a slight increase in proliferative urothelial lesions was found; one male showed papillary hyperplasia and one female exhibited nodular hyperplasia and a papilloma. Our results allow the conclusion that KHCO3, a strong promoter of bladder carcinogenesis, is capable of inducing urinary bladder cancer in rats without prior application of an initiator, whereas KCl, a weak tumour promoter, induced only a few (pre)neoplastic lesions.
Carcinogenesis 1994 Mar
PMID:The role of alkalizing and neutral potassium salts in urinary bladder carcinogenesis in rats. 811 37

We have studied the effect of gastric exposure to 4.5 M NaCl on penetration of a carcinogen, N-[3H]methyl-N'-nitro-N-nitrosoguanidine (3H-MNNG) from the gastric lumen to proliferative cells in the gastric mucosa of Wistar rats at different time intervals after salt exposure. Cells in S-phase were labeled by incorporation of bromodeoxyuridine. Cells in S-phase labeled with 3H-MNNG (double-labeled cells) are the cell population at risk of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis. Ten minutes after salt damage the average percentage S-phase cells labeled with 3H-MNNG in pylorus was significantly decreased compared to control (1.2 +/- 0.6 and 9.5 +/- 0.7). Ten minutes after salt exposure a marked increase in gastric mucosal blood flow and leakage of fluid from the mucosa into the gastric lumen were observed, and the damaged gastric mucosa was covered by a thick mucoid layer. These factors may contribute to the reduced 3H-MNNG penetration into mucosa immediately after damage. Two hours after salt exposure the number of double-labeled cells (8.6 +/- 3.7/mm) and percentage S-phase cells labeled with 3H-MNNG (10.4 +/- 3.1) in pylorus did not differ from control (6.1 +/- 0.9/mm and 9.5 +/- 0.7). Twelve and 24 h after salt exposure the number of double-labeled cells (79.6 +/- 13.4/mm and 32.4 +/- 2.4/mm) and the percentage S-phase cells labeled with 3H-MNNG (29.7 +/- 2.8 and 18.9 +/- 1.3) in pylorus were significantly increased compared to control. Increased number of S-phase cells, a higher location of the proliferative zone in the glandular layer were observed 12-24 h after salt exposure and increased permeability of the mucosa to carcinogen was observed 12 h after salt exposure. These factors explain the increased number of double-labeled cells and the increased penetration of carcinogens to the proliferative cells, and may contribute to explain the previously described cocarcinogenic effect of salt on gastric carcinogenesis.
Carcinogenesis 1994 Apr
PMID:Effect of salt-induced mucosal damage and healing on penetration of N-methyl-N'-nitro-N-nitrosoguanidine to proliferative cells in the gastric mucosa of rats. 814 79

Chlorophyllin (CHL), a water-soluble salt of chlorophyll, has been shown to inhibit 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in vitro by a mechanism that involves molecular complex formation with the carcinogen. Based on this mechanism, rats weighing approximately 160 g were given 10 mumol (100 microCi) IQ or IQ plus 20, 200 or 1000 mumol CHL by single oral gavage. Six hours after dosing, CHL produced dose-related inhibition of IQ-DNA binding in three target organs for carcinogenesis, namely, the small intestine, large intestine and liver. In the latter tissues, > 80% inhibition was detected at the highest CHL dose tested, while IQ-DNA binding levels in the small intestine were reduced to below the limit of detection. Co-injection of CHL and IQ into ligated sections of small intestine inhibited the absorption of IQ in a dose-related manner, such that the highest dose of CHL almost completely blocked carcinogen uptake. Finally, rats given CHL by gavage at time 0 h were treated with IQ at various times thereafter and IQ-DNA binding levels were measured in the liver and colon 6 h after carcinogen exposure. Compared with controls given IQ alone, CHL inhibited binding by 79% at 0 h and 40% at 1 h in the liver, and by 63% at 0 h, 38% at 1 h and 58% at 24 h in the colon (P < 0.05 by Student's t-test). These results support a mechanism involving complex formation between CHL and IQ in vivo and suggest that the inhibitor is likely to be most effective when ingested simultaneously with the carcinogen.
Carcinogenesis 1994 Apr
PMID:Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in rats given chlorophyllin: dose-response and time-course studies in the liver and colon. 814 93

The carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) is enzymatically activated in cells to an ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10- epoxide (BaPDE), which reacts with DNA to form covalent adducts involved in the initiation of cancer. Previously, a post-labeling procedure that uses adenosine-5'-O-(3'-[35S]-thiotriphosphate) was developed to facilitate adduct analysis by HPLC. The much greater carcinogenic potency of (+)-anti-BaPDE makes it essential to be able to separate and identify the adducts formed by all four BaPDE enantiomers in DNA of cells exposed to BaP. Reversed-phase HPLC (RPHPLC) resolved the major (+)-anti-BaPDE-N2-deoxyguanosine [(+)-anti-BaPDE-N2-dG] adduct from the (+)-syn-BaPDE-N2-dG adduct. However, anti-BaPDE-N2-dG adducts formed by (+)- and (-)-anti-BaPDE were not resolved. By using ion-pair RPHPLC (IP-RPHPLC) with tetrabutylammonium phosphate, the [35S]post-labeled (-)-anti-BaPDE-N2-dG adduct eluted 3 min prior to the [35S]labeled (+)-anti-BaPDE-N2-dG adduct. In contrast, the major syn-BaPDE-N2-dG adducts were resolved better by RPHPLC than by IP-RPHPLC. The difference in conditions required for optimal separation of anti- and syn-BaPDE-DNA adducts necessitated the development of an immobilized boronate chromatography technique for the separation of anti- from syn-BaPDE-DNA adducts prior to analytical HPLC analysis. At 4 degrees C and with elution buffers containing high salt concentrations, the [35S]post-labeled anti-BaPDE-DNA adducts were selectively retained by a boronate column whereas the [35S]labeled syn-BaPDE-DNA adducts were not. Analysis of the multiple BaP-DNA adducts formed in BaP-treated hamster embryo cells by these techniques gave results comparable to those obtained by other methods. The major BaP-DNA adducts were anti-BaPDE-N2-dG, 14% from (-)- and 86% from (+)-anti-BaPDE. The ability of these techniques to detect low levels of PAH-DNA adducts because of the high specific radioactivity of 35S and to separate the DNA adducts formed by stereoisomeric PAH diol epoxides adducts by boronate by stereoisomeric PAH diol epoxides adducts by boronate chromatography and HPLC will facilitate studies of the role of individual PAH-DNA adducts in the induction of biological effects such as toxicity and carcinogenesis.
Carcinogenesis 1994 May
PMID:Separation and characterization of post-labeled DNA adducts of stereoisomers of benzo[a]pyrene-7,8-diol-9,10-epoxide by immobilized boronate chromatography and HPLC analysis. 820 94

A 1-ml dose of 4.5 M NaCl was given intragastrically to male Wistar rats at 10 min, 1 h, 4 h, 12 h, 24 h or 48 h before a single intragastric dose of 250 mg/kg N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After 52 weeks the incidence of forestomach squamous cell carcinoma was 21% in control animals receiving MNNG alone. The cancer incidence in the forestomach varied with the time elapsed between application of NaCl and MNNG, and was significantly increased in animals pretreated with NaCl 4 h (43%), 12 h (54%) and 24 h (41%) before MNNG. These results show that salt has a cocarcinogenic effect on initiation of forestomach carcinogenesis in rats, and that this effect depends on the time interval between pretreatment with NaCl and application of MNNG. Gastric adenocarcinomas occurred more frequently in the antrum (78%) than in the corpus (22%). The incidence of gastric adenocarcinoma in animals pretreated with salt before application of MNNG (11%-22%) was not significantly influenced by the time elapsed between pretreatment with salt and application of MNNG, and did not differ from animals receiving MNNG alone (18%). The lack of a cocarcinogenic effect of NaCl on glandular gastric carcinogenesis might be due to the use of dimethyl/sulfoxide as solvent for MNNG.
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PMID:Gastric carcinogenesis in rats given hypertonic salt at different times before a single dose of N-methyl-N'-nitro-N-nitrosoguanidine. 826 12

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2%-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70% of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Influence of sodium butyrate intake on murine colonic carcinogenesis]. 829 30

DNA adducts have been detected in laboratory animals after exposure to carcinogens as well as in human populations with known or suspected risk of developing cancer. Examples are smokers, coke and aluminium workers, urban citizens and roofers. The formation of DNA adducts is an early event in carcinogenesis which can be used for measuring target dose and as a biomarker for genotoxic risk. A method of analyzing 32P-postlabelled DNA adducts on reverse HPLC with on-line detection of 32P has been developed. The method permits direct injection of the 32P-postlabeling mixture into the analytical system without prior purification with background radioactivity on a low level. The method can be used in parallel with TLC analyses of 32P-postlabelled DNA adducts to improve the analytical capacity. The time for analysis of a typical single sample by HPLC and TLC is 30-60 min and 6-24 h respectively. A high (2 M) salt concentration in the HPLC eluent reduces the 32P background considerably. Also the peak tailing was substantially diminished, giving an ability to separate DNA adducts equal to or better than the TLC method. The method has been applied to 2-nitrofluorene (NF), a carcinogenic air pollutant, and N-acetyl-2-aminofluorene (AAF), a model carcinogen which is also a metabolite of NF. A number of DNA adducts are formed in the livers of rats. After oral administration of AAF and NF, DNA adducts in the liver have been characterized as dG-C8-AF and dG-C8-AAF. The major DNA adduct found in both NF- and AAF-administered animals was dG-C8-AF. The described HPLC method can, with minor adjustments, generally be used to analyze 32P-postlabelled DNA adducts.
Carcinogenesis 1993 Jan
PMID:DNA adduct formation after oral administration of 2-nitrofluorene and N-acetyl-2-aminofluorene, analyzed by 32P-TLC and 32P-HPLC. 842 71

Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of hepatocarcinogenesis were examined by monitoring both hepatocyte injury and hepatocellular carcinoma development in F344 rats bearing preneoplastic liver nodules induced by the Cayama-Farber procedure. Redox-enzyme modulation, which included increased cytochrome P450 reductase activity induced by phenobarbital-Na (100 mg/kg, i.p. for 3 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.), depletion of glutathione by phorone (200 mg/kg, i.p.), supplementation with the Fe(III) sodium salt of EDTA (50 mg/kg, i.p.) and redox-cycling activation by menadione (50 mg/kg, i.g.), exerted no prominent hepatocyte injury within nodules but did cause slight injury in the surrounding hepatocytes in nodule-bearing rats. The same treatments induced severe hepatocyte injury in non-treated normal rats. Redox-enzyme modulation performed every other week for 33 weeks significantly reduced the number of hepatocellular carcinomas developing in nodule-bearing rats. These results indicate that preneoplastic nodules are resistant to the oxidative stress induction caused by redox-enzyme modulation treatment and that, despite toxic effects in surrounding hepatocytes, no progression pressure is exerted. Indeed, the treatment rather demonstrates an inhibitory effect of the evolution of the nodules into hepatocellular carcinomas.
Carcinogenesis 1993 Jan
PMID:Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of rat hepatocarcinogenesis. 842 75


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