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

There are divergent opinions on the effect of ethanol in the carcinogenesis of gastroduodenal tumors. The effect of the synchronous application of 11% ethanol or wine (11% ethanol) and N-methyl-N'-nitro-N-nitrosoguanidine (100 micrograms/ml, MNNG) in a drinking solution on the incidence of gastroduodenal tumors was evaluated. Sixty outbred male Wistar rats were distributed among three groups. The animals drank MNNG and ethanol or wine for six months and consumed the same quantity of MNNG. Then they consumed a normal diet until the 13th month, when the experiment was terminated. The stomach and duodenum were examined histologically. In the stomach, 15 tumors (2 squamous paillomas, 4 squamous carcinomas, 1 sarcoma, and 8 adenocarcinomas) and 4 cases of dysplasia were found; in the duodenum, there were four cases of adenocarcinoma. There were 6 cases of multiple tumors. Incidence of forestomach tumors did not differ among the groups, whereas the incidence of glandular stomach carcinoma and duodenal carcinoma was significantly lower in the groups treated with 11% ethanol or wine than in the control group. MNNG was not inactivated by ethanol in the drinking solutions. We concluded that the inhibitory effect on gastroduodenal carcinogenesis is the result of 11% ethanol ingestion and its protective action on the mucosa and not of the wine's nonethanol components.
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PMID:Inhibition of MNNG-induced gastroduodenal carcinoma in rats by synchronous application of wine or 11% ethanol. 891 Sep 16

Sarcomas have been shown to develop next to foreign body implants, silicone included, in animal experiments. However, this carcinogenesis is not believed to have any human relevance. A review of the existing epidemiological studies suggests that women with silicone breast implants have a reduced risk for developing breast cancer. However, the presence of breast implants does obscure mammographic visualization as well as palpation of mammary tissue. This has led to the assumption that breast cancer detection could be compromised in women with breast implants. In the few studies that have dealt with this issue, women with breast implants were diagnosed with the same stage of disease as women without implants. However, the percentage of false negative mammographies was increased in one study. In conclusion, there is currently no evidence of an association between breast implants and cancer or postponed breast cancer detection.
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PMID:[Silicone breast implants and breast cancer]. 923 41

Sarcoma may arise on unabsorbable foreign bodies in rodents and more rarely in man. Perforations of the implant reduce its carcinogenicity so that nitrocellulose filters of pore size 0.45 micron have failed to induce tumour. We examined whether increase of surface area would restore carcinogenesis to film with such pore size. Nitrocellulose filters of 25 mm diameter and pore size 0.45 micron were implanted singly, in pairs and in trios subcutaneously in 3 respective groups of BALB/c mice (total 97) and observed for sarcomagenesis for 100 weeks. No tumour arose on the singles (surface area 0.98 mm2), while 7 arose on the paired (1.96 mm2) at a mean of 54 weeks and 16 on the trios (2.95 mm2) at a mean of 46 weeks (differences significant at p > 0.01). A sufficiency of surface area restores carcinogenicity to perforated foreign surfaces in mice. Surface area is dominant over film perforation size in film sarcomagenesis.
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PMID:Effect of film size on production of foreign body sarcoma by perforated film implants. 942 73

A new approach to analyze the p53 mutation database of the European Molecular Biology Laboratory for a comparison of mutation spectra is described, with the aim of investigating organ specificity of etiological factors and putative organ-to-organ relationships in cancer pathogenesis. The number of entries of each nucleotide- and base-pair substitution-specific mutation was divided by the total number of tumors analyzed. For each organ pair, the difference of the mutation-specific frequency differences was calculated. Resulting values could range from 0 (full concordance) to 2 (full discordance). Skin, lung, and urinary bladder showed highly independent mutation spectra (maximum discordance value = 1.48 for skin versus brain), in agreement with the presence of specific factors responsible for a large number of the respective tumors (UV light, smoking, aromatic amines). The three organs with the smallest sum of discordance values were mammary gland (breast), colon and esophagus. The minimum organ-to-organ discordance value was 0.95, for stomach versus colon. For these organs, common, possibly also endogenous, cancer risk factors could be postulated as contributing to the observed mutation spectrum. The remaining cancers (ovary, sarcoma, leukemia/lymphoma, brain, head and neck, and stomach, in order or increasing discordance) were of intermediate range and showed a mix of values. Reasons for close relationship to some of the other organs and marked differences to others are discussed. Exclusion of the "hot-spot" mutations did not markedly alter the observed relationships, indicating that a putative selective growth advantage does not cover up the etiological basis for the observed mutation spectrum. It is expected that much more insight into carcinogenesis and cancer could be gained by further exploratory analyses of mutation databases.
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PMID:Position- and base pair-specific comparison of p53 mutation spectra in human tumors: elucidation of relationships between organs for cancer etiology. 949 24

The expression of Bfl-1 gene, a novel Bcl-2 related gene, was determined by Northern blot analysis using a radiolabeled cDNA specific for Bfl-1 gene in 82 surgically resected tissue specimens of 28 gastric cancers, 15 colon cancers, nine breast cancers, eight bone and soft tissue sarcomas, five ovarian cancers, nine colon adenomas and eight gastric adenomas. A high rate of expression was observed in gastric and colon cancer, at 86 and 93%, respectively. In breast cancer, bone and soft tissue sarcoma and ovarian cancer, the expression rate was 33, 25 and 40%, respectively. In stomach cancer, the expression rate of Bfl-1 gene in metastatic lymph nodes was 82%, which was higher than 50% of the primary sites (p < 0.02). The intensity of RNA bands of the gastric cancer specimens was compared according to the stage, demonstrating that there was no difference in the expression levels of Bfl-1 gene between the stages in both primary sites and metastatic lymph nodes. Bfl-1 gene was expressed in three (33%) out of nine adenomas of the colon, while it was not detected in all eight gastric adenomas, We also examined the RNA expression of Bfl-1 gene in 22 human cancer cell lines consisting of five stomach cancer, four squamous cell carcinoma, three lung cancer, three cervical cancer, two colon cancer, two brain cancer, two leukemia and one osteosarcoma cell lines. Bfl-1 gene band was detected in one (5%) cervical cancer cell line, SiHa. The results of cancer tissue specimens indicate that Bfl-1 gene may play an important role in carcinogenesis of human cancers and may be involved in a relatively early phase of the adenoma-carcinoma sequence in colon cancer development. However, the mechanism responsible for the very low rate of expression in established cell lines is not clearly understood and further investigation is necessary to clarify the mechanism involved.
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PMID:Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines. 949 79

Carcinogenesis of 35 ddy male mice submandibular salivary glands were attempted; using implants of a 1 mg (2 mm) prepared pellets of the potent chemical carcinogen 9, 10-dimethyl-1, 2-benzanthracene (DMBA) dry powder without a vehicle or carrier. This method appeared to be easy, fast and effective. Within a period ranging from 7-14 weeks; twenty animals developed epidermoid carcinoma (two of them developed squamous cell carcinoma of covering skin as well), and two animals developed mixed tumors (pleomorphic adenoma like tumor) but neither adenocystic carcinoma nor sarcoma were found, the results were adequately discussed.
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PMID:Carcinogenesis of mouse submandibular salivary gland using DMBA implant. 949 56

Polychlorinated dibenzo-p-dioxins (PCDDs), commonly known as dioxins, form as unwanted impurities in the manufacturing of chlorophenol and its derivatives--pulp and paper--and in the combustion of municipal, sewage-sludge, hospital, and hazardous waste. Combustion, in presence of a chlorine donor, seems to be a major source of these compounds. High levels of dioxins are also emitted from metallurgical industries including copper smelters, electric furnaces in steel mills, and wire reclamation incinerators. Trace levels are detectable in emissions from motor vehicles using leaded gasoline or diesel fuel, in forest fires, and in residential wood burning. Extremely persistent and widely distributed in the environment, PCDDs have been detected in all three primary and many secondary media. Releases into the air occur mainly from combustor emissions. Atmospheric dispersion, deposition, and subsequent accumulation in the food chain seem to be the major pathways of exposure to the general population. Residues of these chemicals have been detected in soil, sediment, fish, meat, cow's milk, human adipose tissue, and mothers' milk. In general, these chemicals have high lipophilicity. The elimination half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans is approximately 7-11 years. Very little human toxicity data from exposure to PCDDs are available. Health-effect data obtained from occupational settings in humans are based on exposure to chemicals contaminated with TCDD. It produces a spectrum of toxic effects in animals and is one of the most toxic chemicals known. Most of the toxicity data available on TCDD are from high-dose oral exposures to animals. Very few percutaneous and no inhalation exposure data are available in the literature. There is a wide range of difference in sensitivity to PCDD lethality in animals. The signs and symptoms of poisoning with chemicals contaminated with TCDD in humans are analogous to those observed in animals. Dioxin exposures to humans are associated with increased risk of severe skin lesions such as chloracne and hyperpigmentation, altered liver function and lipid metabolism, general weakness associated with drastic weight loss, changes in activities of various liver enzymes, depression of the immune system, and endocrine- and nervous-system abnormalities. It is a potent teratogenic and fetotoxic chemical in animals. A very potent promoter in rat liver carcinogenesis, TCDD also causes cancers of the liver and other organs in animals. Populations occupationally or accidentally exposed to chemicals contaminated with dioxin have increased incidences of soft-tissue sarcoma and non-Hodgkin's lymphoma. No comprehensive studies have been conducted to determine any health impact to the general population from environmental exposure to PCDDs. This paper presents a brief review of relevant animal and human data for projecting any possible health effects from environmental exposures to PCDDs.
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PMID:Health impact of polychlorinated dibenzo-p-dioxins: a critical review. 951 23

Endothelial cell biology has recently been the subject of considerable interest in thrombosis and cancer research. However, the successful establishment of immortalized human endothelial cells which retain differentiated cell characteristics has been rare. We have successfully established immortalized human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16 E6-E7. HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells. Both E6 and E7 cultures had an extended lifespan but eventually underwent senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in culture but did not undergo malignant conversion. Telomerase activity was not detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4-5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial origin. The line expressed integrin subunits (alpha(v)beta3, alph(v)beta5, beta1, alpha2, alpha3, beta4 and alpha6) consistent with an endothelial origin. The higher passage of 4-5-2G line showed a similar intensity of integrin immunostaining to that of primary HUVECS. Subsequent infection of these immortal cells with the Kirsten murine sarcoma virus which contains an activated K-ras oncogene induced morphological transformation that led to the acquisition of invasion capability and neoplastic properties. Telomerase was also detected in the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful for studies of the molecular mechanisms underlying normal and neoplastic endothelial cell proliferation and migration, and might also provide an in vitro model for development of pharmacologic and gene therapy for cardiovascular thrombosis and cancer.
Carcinogenesis 1998 Apr
PMID:A human vascular endothelial cell model to study angiogenesis and tumorigenesis. 960 Mar 54

Although data on genetic alterations leading to the development of colorectal cancer are abundant, no specific genetic alteration, as has been demonstrated for certain rare tumors such as lymphoma, leukemia, or sarcoma, has been shown to be responsible for the development of colorectal carcinomas. The colorectal cancer phenotype undoubtedly originates from an accumulation of different genetic alterations. The nature of these alterations, their order of appearance, and their associations vary greatly from one tumor to another, suggesting that the concept of a unique model of carcinogenesis is not applicable to these tumors. We studied a panel of 40 colorectal tumors in an attempt to identify different carcinoma subsets distinguishable by the pattern of genetic alterations. We examined a series of genetic anomalies frequently implicated in the development of colorectal cancer, including genetic material loss, demonstrated by loss of heterozygosity on chromosome arms 1p, 17p, and 18q; mutations of proto-oncogene K-RAS codons 12, 13, and 61; and gene TP53 mutations, identified by studying the accumulation of the corresponding immunohistochemically detectable protein. Our findings showed an important correlation between the genetic material loss events and an independent distribution of point mutations, which favors the hypothesis of a specific type of genetic instability characterized by the recurrent loss of chromatin fragments implicated in a subset of colorectal cancers.
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PMID:Genetic alterations in colorectal cancer, comparative analysis of deletion events, and point mutations. 964 55

An understanding of the basic mechanisms responsible for the pathogenesis of liver neoplasms is needed in order to develop better therapeutic strategies. The present study utilized a pharmacogenetic mouse model to assess the role of cytochrome P4501A1 (Cyp1a1) in modulating genetic damage to oncogenic and tumor suppressor loci following in utero exposure to the polycyclic aromatic hydrocarbon, 3-methylcholanthrene (MC). Analysis of the Ha-ras, Ki-ras, INK4a and p53 genes was carried out with lysates from paraffin-embedded liver tissue from transplacentally-treated mice. The lysates were subjected to DNA amplification by the PCR technique followed by allele-specific oligonucleotide hybridization screening and SSCP analysis. All of the 26 neoplasms screened (23 hepatocellular carcinomas, two hepatocellular adenomas and one sarcoma) exhibited a GGC-->CGC (GLY13-->ARG13) transversion at the Ki-ras gene locus. None of the tumors had Ki-ras mutations at codon 12 of exon 1. Approximately 12% (3/26) of the liver tumors exhibited point mutations in exon 1 of the INK4a gene, with each of the three tumors exhibiting two point mutations. Analysis of exon 2 of the INK4a gene showed the presence of a CCG-->CTG (PRO73-->LEU73) transition in two of the 26 neoplasms. No mutations were found in exons 1 or 2 of the Ha-ras gene, or in exons 5-8 of the p53 gene. Analysis of tumor RNAs showed overexpression of Ha-ras, cip1 and c-jun in approximately 38% of the liver tumor samples. The results of this study suggest that mutagenic damage to oncogenes and tumor suppressor genes may be critical factors in mediating transplacentally-induced liver tumorigenesis. The fact that Ki-ras mutations were found in all of the tumors suggests that mutation at this gene locus may be an early event in liver tumor pathogenesis, while mutation in tumor suppressor genes may occur later during tumor progression. These combined results are consistent with the pathogenesis of cancer in humans.
Carcinogenesis 1998 Jun
PMID:Induction of mutations in Ki-ras and INK4a in liver tumors of mice exposed in utero to 3-methylcholanthrene. 966 43


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