Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that the endogenous nitrosation of aliphatic, cyclic and heterocyclic secondary amines in the urinary bladder of patients with chronic urinary bacterial infections and in the human stomach may provide an important additional source of exposure to carcinogenic volatile N-nitrosamines. The most commonly occurring nitrosatable secondary amines found in human saliva, gastric juice, blood, urine and faeces are dimethylamine (DMA), pyrrolidine (PYR) and piperidine (PIP). All of 40 analysed samples of gastric juice contained 0.87 +/- 0.89 (SEM) microgram/ml DMA, 39 contained 1.35 +/- 2.53 microgram/ml PIP, 36 contained 0.18 +/- 0.15 microgram/ml PYR and 14 contained 0.05 +/- 0.11 microgram/ml diethylamine. Nitrate (14.0 +/- 15.7 microgram/ml) was present in all samples and 11 of 40 samples contained 0.43 +/- 1.38 microgram/ml nitrite. Only one gastric juice sample with pH less than 4.5 contained nitrite (0.1 microgram/ml). In paraplegics, patients with bladder augmentations and two control groups without bacterial infections of the urinary bladder, a mean daily excretion of 40.5-49.7 mg/day DMA, 19.4-23.8 mg/day PYR and 26.1-31.7 mg/day PIP was found. In both patient groups suffering from chronic bacterial infection of the urinary bladder, the corresponding volatile N-nitrosamines were formed by endogenous nitrosation and excreted in urine.
Carcinogenesis 1992 Apr
PMID:Secondary amine precursors to nitrosamines in human saliva, gastric juice, blood, urine and faeces. 157 7

Radioimmunoassays (RIAs) have been used to detect the promutagenic lesion O6-methyldeoxyguanosine (O6-MedG) in DNA isolated from the bladder tissues of Egyptian patients presenting with bladder carcinoma and concomitant schistosomiasis (bilharziasis), a parasitic disease known to be associated with the presence of N-nitrosamines in the urine. Alkylation damage was present in the DNA of the majority of the samples (44/46, 96%); 38 samples were of tumour tissue and 8 from uninvolved bladder mucosa. Levels of O6-MedG ranged from undetectable (ND; i.e. less than 0.01 mumol O6-MedG/mol dG) to 0.485 mumol/mol dG with an overall mean of 0.134 +/- 0.10 mumol/mol dG, including the two samples that were below the limit of detection. In contrast, methylation damage was detected in only 4/12 (33%) of the DNA samples from normal bladder tissue of European origin. In these samples levels of O6-MedG ranged from ND to 0.225 mumol/mol dG with an overall mean of 0.046 +/- 0.082 mumol O6-MedG/mol dG. These results confirm that alkylation events can be detected in the DNA of schistosome-infected human bladder tissue. The methylation of uninvolved and tumour tissue DNA to similar extents suggests that the alkylating intermediate may have been present in the urine. These results indicate the need for further investigation to determine whether relationships exist between levels of DNA damage and the prevalence of schistosome infection and/or the extent and type of bacterial infection that frequently accompanies this disease.
Carcinogenesis 1992 May
PMID:Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals. 158 2

Human exposure to endogenously formed N-nitroso compounds has frequently been suggested as a causative factor in carcinogenesis where this is related to chronic bacterial infection such as is seen in gastric achlorhydria. At least two distinct mechanisms of endogenous formation have been identified. The first, a direct chemical reaction between secondary amino compounds and nitrite, is strongly pH dependent and does not proceed rapidly at neutral pH even in the presence of chemical catalysts. The second depends on the direct bacterial catalysis of N-nitrosation. The data presented demonstrate that the bacterially mediated reaction is catalysed by bacterial enzyme systems and proceeds much more rapidly at neutral pH than the chemical reaction. This suggests a particular relevance to the in vivo situation where neutral pH, bacteria and elevated nitrite concentrations are found. Drawing on the kinetic information presented regarding the bacterially mediated nitrosation reaction, the known kinetics of the chemical reaction and the published values for the relevant substrate concentrations in both the colonised and the normal acid stomach the bacterial and chemical reactions have been compared. Using these criteria, and assuming the presence of bacteria with the appropriate metabolic activity, it may be predicted that N-nitroso compounds may be formed in the colonized stomach at much higher concentrations than in the normal acid stomach. The difference in yield may be by two to four orders of magnitude. Different bacterial species and different isolates of the same species show considerable variation in their abilities to catalyse N-nitrosation reactions. The most rapid catalysis is associated with those bacteria capable of reducing nitrate and nitrite by the process of denitrification. The most significant clinical corollary of these studies is that although bacterial catalysis of N-nitrosation has been demonstrated unequivocally, bacterial colonization of the stomach may not itself necessarily result in elevated endogenous N-nitroso compound exposure despite the elevated nitrite concentrations normally associated with such colonization. An increase in exposure to endogenously formed N-nitroso compounds would only be predicted in those individuals where a significant proportion of the colonizing bacteria expressed significant N-nitrosation activity. As a consequence the carcinogenic risk may be restricted to only a small proportion of colonized individuals depending on the prevalence of sustained infection by bacteria with significant N-nitrosation activity, particularly denitrifiers.
Carcinogenesis 1987 Dec
PMID:Bacterially catalysed N-nitrosation reactions and their relative importance in the human stomach. 311 47

Experimental introduction of Escherichia coli type 04 into the subserosa of the urinary bladder of female Fischer 344 rats produced chronic bacterial infection in more than 90% of animals. Groups of rats with bacterial infection were given sodium nitrate and either piperazine (Group 1) or dibutylamine (Group 2) in the drinking-water. Control, noninfected animals received nitrate and either piperazine (Group 3) or dibutylamine (Group 4). At 40 weeks, transitional-cell carcinomas of the bladder were detected in 9/30 rats in Group 1 compared to 0/34 in Group 3 (p less than 0.0005), and in 11/34 rats in Group 2 compared to 0/32 in Group 4 (p less than 0.0003). Early changes were examined by scanning and transmission electron microscopy as well as autoradiography. Preneoplastic liver foci were detected in infected groups of animals receiving amine and nitrate, indicating reabsorption of the carcinogen synthesized in situ to induce distant organ transformation. In another experiment, E. coli infection augmented bladder carcinogenesis by N-nitrosobutyl(4-hydroxybutyl)amine (NBHBA), as indicated by earlier appearance of bladder tumours (six weeks compared to nine weeks) and, after 25 weeks, higher incidences of transitional-cell carcinomas (41/46 compared to 39/53, p less than 0.05), squamous metaplasia (43% compared to 9%, p less than 0.0001), glandular metaplasia (26% compared to 13%, p less than 0.05) and muscle invasion (30% compared to 11%, p less than 0.01) in the E. coli-infected group receiving carcinogen compared to the noninfected group receiving carcinogen, respectively. These results indicate that bacterial infection of the urinary bladder may play a major role in bladder carcinogenesis, both by helping in-situ nitrosamine synthesis and by augmenting carcinogenesis by nitrosamines.
 ...
PMID:Escherichia coli infection of the urinary bladder: induction of tumours in rats receiving nitrosamine precursors and augmentation of bladder carcinogenesis by N-nitrosobutyl (4-hydroxybutyl)amine. 331 99

In Egypt, bladder cancer incidence is high in areas where the prevalence and intensity of Schistosoma haematobium infection is also high. Experimental evidence shows bladder carcinogenesis to be a multi-stage process which can be accelerated by many factors. N-nitroso compounds, some of which are known bladder carcinogens, can be formed from amine precursors and nitrate in urine during some bacterial infections. In experimental animals the growth of nitrosamine-induced urothelial cancers is accelerated by damage to the urothelium caused by S. haematobium infections, and by analogy in man this could account for the lower peak age of incidence of this cancer in Egypt by comparison with Europe. The present study was designed to investigate whether bacterial infection of the urinary tract was common in areas of endemic schistosomiasis and whether N-nitrosamines were regularly found to be associated with bacteriuria. Urine samples from young men in the Qalyub area of Egypt and from an adjacent Delta region were analysed for S. haematobium ova, the nature and intensity of any bacterial infection, nitrate and nitrite, and total N-nitroso compounds plus volatile N-nitrosamines. A relatively high prevalence of bacteriuria was found in young men with schistosomiasis and low levels of N-nitroso compounds were present in all specimens. When the groups were sub-divided on the basis of the ability of their bacterial flora to reduce nitrate to nitrite (the latter is required for the nitrosation of amine precursors to N-nitroso compounds), significantly higher levels of N-nitroso compounds were found in S. haematobium-infected individuals also infected with nitrate-reducing bacteria by comparison either with uninfected controls (p less than 0.0005) or with those infected with non-nitrate-reducing bacteria (p less than 0.001). The results show N-nitroso compounds to be present in the urines of young men in areas of endemic S. haematobium infection in Egypt, and elevated levels of urinary N-nitroso compounds to be associated with infection of the urinary tract by various species of nitrate-reducing bacteria.
 ...
PMID:Association of bacteriuria and urinary nitrosamine formation with Schistosoma haematobium infection in the Qalyub area of Egypt. 692 71

Urinary nitrite was present in 5.6% of 2379 individuals from a rural population infested with "Schistosoma haematobium". A higher frequency was observed in symptomatic patients with active bilharzial cystitis (25%) and patients with bladder cancer associated with schistosomiasis (66.2%); conversely, urinary nitrite was absent in normal urban individuals. The frequency of urinary nitrite was higher in females (6.4%) than males (4.6%), and was more frequent in adults than extremes of age. The presence of urinary nitrite was associated with urinary infection and was commonly accompanied by cellular atypia in urine, in the form of dysplasia. Under these circumstances, carcinogenic nitrosamines are liable to be produced in the bladder from urinary nitrite and amines. These observation support the possible role of urinary bacterial infection, commonly associated with bilharzial cystitis, in bladder carcinogenesis.
 ...
PMID:A study on the etiological factors of bilharzial bladder cancer in Egypt: 5-urinary nitrite in a rural population. 741 6

Gastric atrophy and intestinal metaplasia are considered the earliest phenotypic changes in the cascade of events leading from normal mucosa to intestinal-type gastric cancer, and epidemiological evidence links Helicobacter pylori to gastric epithelial malignancies. To evaluate any causal relationship between bacterial infection and atrophic metaplastic lesions, gastric pathology was histologically and histochemically evaluated in 267 consecutive, nonulcerous, untreated subjects, with attention given the phenotypes of intestinal metaplasia. The prevalence of Helicobacter pylori infection was 61%. Intestinal metaplasia (particularly types II and III) was significantly associated with both Helicobacter pylori detection (chi 2 LR: P < 0.002) and increasing age (chi 2 LR: P < 0.002). Using logistic regression analysis, the development of intestinal metaplasia proved more significantly linked with Helicobacter pylori infection [odds ratio = 4.55 (95% confidence interval: 1.51-13.7)], than with age [odds ratio = 1.03 (95% CI: 1.01-1.06)], with no interaction. In conclusion, Helicobacter pylori can be considered among the major causal agents of mucosal lesions involved in the multistep process of gastric carcinogenesis, justifying any attempt to eradicate this bacterial infection.
 ...
PMID:Helicobacter pylori in promotion of gastric carcinogenesis. 862 68

Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Helicobacter pylori infection. H. pylori has been epidemiologically linked to adenocarcinoma of the distal stomach by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds. H. pylori is the first bacterium to be termed a definite cause of cancer in humans by the International Agency for Research on Cancer. Mutagenic bacterial metabolites are also suspected to increase risk for cancer. This model is best exemplified in colon cancer. Bile salt metabolites increase colonic cell proliferation. Exogenous compounds such as rutin may be metabolized into mutagens by resident colonic flora. Moreover, Bacteroides species can produce fecapentaenes, potent in vitro mutagens, in relatively high concentrations. In vivo data on human carcinogenesis by bacterial metabolites, however, are inconsistent. Local bacterial infections may also predispose to nonnodal lymphomas, although the mechanisms for this are unknown. Gastric lymphomas and immunoproliferative small intestinal disease have been most strongly linked to underlying bacterial infection. Because bacterial infections can be cured with antibiotics, identification of bacterial causes of malignancy could have important implications for cancer prevention.
 ...
PMID:Bacterial infection as a cause of cancer. 874 96

A rare case is presented of a 57-year-old Japanese male with synchronous and metachronous multicentric squamous cell carcinomas (SCC) in the upper aerodigestive tract. During a 9-year-period from the appearance of first primary SCC to autopsy, 14 foci of primary SCC and one severe dysplasia developed in succession in the thoracic esophagus, oral floor, soft palate, uvula, lingual radix, piriform recess, hypopharynx, cervical esophagus, trachea and lingual body. The patient died of severe bronchopneumonia due to Gram-negative bacterial infection that developed as a result of recurrent nerve paralysis. Human papilloma virus and Epstein-Barr virus, which are risk factors, were not detected by immunohistochemistry or by the polymerase chain reaction method. Genetic analysis revealed the absence of point mutations in K-ras codon 12. Heavy consumption of alcohol and excessive smoking may have been responsible for the multicentric carcinogenesis. This is the first case report in the literature of the development of so many primary SCC lesions in the upper aerodigestive tract during such a short period.
 ...
PMID:Synchronous and metachronous multicentric squamous cell carcinomas in the upper aerodigestive tract. 905 95

Helicobacter hepaticus is a recently discovered bacterium that invades mouse liver causing chronic active hepatitis followed by development of preneoplastic hepatocellular foci, hepatocellular adenomas and carcinomas. This establishes a unique animal model for study of the mechanisms of cancer development due to a chronic bacterial infection. A possible mechanism of bacteria-associated tumorigenesis is mutation of oncogenes or tumor suppressor genes. Since mutations in ras oncogenes have been widely detected in a variety of chemically induced and spontaneous mouse liver tumors and specific mutations in the p53 tumor suppressor gene have been associated with human bladder cancers attributed to chronic schistosomal infection, we studied exons 1 and 2 of the N-, K- and H-ras genes and exons 5-8 of the p53 gene for the presence of point mutations in 25 liver tumors from 10 naturally infected A/JCr mice, ranging in age from 16 to 24 months. The 20 adenomas and five carcinomas varied in size from 0.1 to 2.3 cm and arose in livers characterized by a wide assortment of pathological profiles, including hepatitis, inflammation, hyperplasia, hypertrophy, leukocyte infiltration, necrosis and focal phenotypic alteration. DNA samples extracted from formalin-fixed paraffin-embedded tissues were screened by PCR/SSCP analysis and showed no mutations in the analyzed genes. Complete absence of mutations in ras genes in 25 mouse liver tumors is unusual. Other genes may be targeted or H. hepaticus infection causes liver cancer through other pathways than direct damage to DNA.
Carcinogenesis 1997 Jan
PMID:Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice. 905 12


1 2 3 4 5 6 Next >>