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

The susceptibility of healed, experimental gastric ulcers to chemical carcinogenesis was investigated. Slowly healing gastric ulcers were induced by the acetic acid method in the fundic and pyloric gastric mucosae of inbred male Wistar rats. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water at a concentration of 50 mg/liter for 360 days after ulcer induction. Twenty-eight adenomatous hyperplasias and six-adenocarcinomas developed in the pyloric mucosae of rats, including five cases of adenomatous hyperplasia which developed in the periphery of the healed ulcer. In contrast, only one adenomatous lesion was found in the regenerated mucosa of the healed pyloric ulcer. No neoplasm was observed in the healed fundic ulcer area. The results demonstrated an increased incidence of neoplasms in the peripheral area of the healed pyloric ulcer and a decreased incidence of neoplasms in the regenerated mucosa within the healed pyloric ulcer scar, although these differences were not statistically significant in comparison with the intact pyloric mucosae of the MNNG-treated rats. Histoautoradiographs of the gastric mucosae demonstrated increased labeling indices in the healed ulcer periphery of the pyloric mucosa and decreased labeling indices in the regenerated mucosa within the healed pyloric ulcer scar of MNNG-treated rats, which might be related to the differential susceptibility of the two regions to gastric carcinogenesis. Intestinal metaplasia preferentially developed near the pyloroduodenal junction in MNNG-treated rats but was not localized in control rats. In the fundic ulcer scar area, an unusual squamous cell metaplasia was observed in one rat.
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PMID:Susceptibility of healed gastric ulcers to chemical carcinogenesis in rats and implications of cellular kinetic changes. 649 43

We have recently shown that a variety of human tumor cell lines are capable of preventing chloroethylnitrosourea (CNU)-induced DNA crosslinks, presumably by removing guanine O6-chloroethyl DNA monoadducts before crosslinks can form. Those cells capable of preventing crosslinking were of the Mer+ (Methylation repair) phenotype, and have been shown to be proficient at repair of O6-methyl-guanine adducts by the repair enzyme guanine-O6-methyl-transferase. Mer- tumor cell lines are: deficient at O6-methyl-guanine repair, incapable of preventing CNU interstrand crosslinking, and have recently been shown to lack the repair enzyme O6-methyl-transferase. We wish to report that pretreatment of Mer+ cells (HT-29 human colon carcinoma cells and IMR-90 normal human fibroblasts) with the DNA methylating agent MNNG, under conditions which should inactivate O6-methyl-transferase, apparently saturates the monoadduct repair system, and allows CNU to form interstrand crosslinks in these cells. This effect was also seen when MNU pretreatment was used, but not with MMS or streptozotocin. The formation of CNU-induced interstrand crosslinks following MNNG or MNU pretreatment was coincident with a dramatic increase in cytotoxicity as measured by colony formation assays. In contrast, cytotoxicity was only slightly increased when MMS or streptozotocin pretreatment was used.
Carcinogenesis 1984 Jan
PMID:Pretreatment of human colon tumor cells with DNA methylating agents inhibits their ability to repair chloroethyl monoadducts. 669 90

Three epithelioid cell lines were initiated from stage 35 tadpoles of Xenopus borealis. Cell strain XB693-M1 was obtained by incubation of one of these cell lines in MNNG. The strain is hypotetraploid with a modal chromosome number of 62. It is tumorigenic when 4 X 10(6) cells are injected into hosts belonging to a partially histocompatible family. The tumors are very invasive, metastasizing adenocarcinomas that kill the host within 5 to 38 weeks. The tumor can be propagated in vivo by serial transplantation.
Carcinogenesis 1983
PMID:An oncogenic cell line inducing transplantable metastasizing adeno-carcinomas in Xenopus borealis. 686 Dec 77

Modifiers of gastric carcinogenesis are reviewed with evidence of experimental results using rats. 1) Physical modifiers: Route of administration, medium (vehicle) of carcinogens, detergents, dosage (concentration), period (frequency) of administration, exposure time, and condition of mucus. Effects of surfactants and presence of a foreign body in the stomach lumen are also samples of physical enhancing factors. 2) Biological modifiers: Species, genetics, sex, hormonal factors, nutrition, and age. Moreover, effect of preexisting ulceration is important. 3) Chemical modifiers: Chemical substances administered prior to, simultaneously with, or following exposure of experimental animals to chemical carcinogens, or promoters of carcinogenesis. Chemical modifiers are: co-initiators, tumor promoters and inhibitors. NaCl having both co-initiator and tumor promoter action on MNNG gastric carcinogenesis is clearly shown in our investigations.
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PMID:[Experimental carcinogenesis of the stomach and its modifiers]. 688 83

A gastroenterostomy without entero-anastomosis in rats favours the development of adenomatous epithelial lesions at the gastroenteral borderline in dependence of exposition to MNNG. The extent of such changes in the mucosa could be modified by vagotomy, pyloroplasty, or the prevention of duodenogastric reflux (Roux-en-Y method), whereby vagotomy has an enhancing effect on proliferation. A comparison of the mucosal changes at the gastroenteral anastomosis indicates that a multitude of factors causes environmental changes at the gastroenteral borderline, stimulating epithelial proliferation to the point of cancer formation. Thus, it is not possible to accuse any single factor such as intestinal reflux, carcinogens or different surgical techniques as the sole culprit in carcinogenesis.
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PMID:Frequency of cancerous and precancerous epithelial lesions in the stomach in different models for enterogastric reflux. 694 98

We have provided experimental evidence in favour of the hypothesis that carcinogenesis is triggered by at least two chromosomal events, which must occur in a single diploid somatic cell in a specific time sequence: (i) specific recessive mutational or epigenetic chromosomal change(s) resulting in a heterozygous (m/+), latently premalignant state (initiation); this must be followed by (ii) a chromosomal rearrangement involving the affected locus, and leading to homozygosity (m/m) or hemizygosity (m/o), and subsequent expression of the recessive malignant character (promotion). The complete carcinogen, MNNG, induced mutations (6-thioguanine-resistance), chromosomal rearrangements and SCEs in V79 Chinese hamster cells. TPA, a potent tumour promoter, induced only SCEs and specific chromosomal effects. Antipain, a protease inhibitor and a known inhibitor of both carcinogenesis and tumour promotion, inhibited only the MMNG-induced chromosomal rearrangements (but not mutagenesis and SCEs) and the TPA-induced chromosomal events. These results suggest that (1) both TPA-induced and MNNG-induced chromosomal rearrangements are caused by the activation or induction of mitotic recombination and hence appear to be preventable; (2) chromosomal rearrangement is a rate-limiting step in carcinogenesis; and (3) if mutagenesis is involved in carcinogenesis, it is probably not sufficient. The existence of the human cancer-prone syndromes, Bloom's, Fanconi's anaemia and ataxia telangiectasia, which involve spontaneous chromosomal rearrangements analogous to those induced by carcinogens in normal cells, strongly supports our hypothesis that carcinogenesis involves two chromosomal events. We discuss the implications of this work to carcinogenicity testing and cancer prevention strategies.
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PMID:Chromosomal events in carcinogenic initiation and promotion: implications for carcinogenicity testing and cancer prevention strategies. 700 84

Quantitative analysis of intestinal microflorae in the diverted and feces-containing portions of the colon after performing an ascendo-descendostomy Roux en Y in Wistar-Lewis rats, the colonic portion from the ascending colon to the midportion of the descending colon being diverted from the fecal stream, disclosed a drastic decrease in the total amount of the intestinal microflora as well as most anaerobic microflorae in the diverted portion of the colon where the amount of the colonic content was extremely reduced. This diverted segment was least susceptible of developing macroscopical epithelial neoplasia after exposure to a carcinogen, MNNG, sufficient in amount to evoke multiple large neoplasia in the ordinary colon, although microscopical intramucosal neoplastic foci were induced there. Thus the existence of the intestinal content was essential for the process of promotion in experimental colonic carcinogenesis. The close parallelism between amounts of intestinal content and amounts of intestinal microflorae, especially anaerobic ones, suggested the roles of anaerobic microflorae in colonic carcinogenesis.
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PMID:Amounts of intestinal microflorae in relation to colon carcinogenesis. An experimental study. 738 Jan 70

cDNA for mouse O6-methylguanine-DNA methyltransferase was expressed in methyltransferase-deficient Escherichia coli mutant cells, and the overproduced mouse enzyme was purified to a homogeneous state. Using this purified product, polyclonal antibodies were prepared and used to estimate amounts of the methyltransferase protein in cells. A single cell of NIH3T3 contained 1.8 x 10(4) molecules of the methyltransferase protein. When mouse fibroblasts were immunostained, it was shown that most of the methyltransferase protein exists in the cytoplasm rather than in the nucleus. Using double-stranded oligomers containing a single O6-methylguanine or O4-methylthymine at predetermined sites, the mouse enzyme repaired O6-methylguanine and O4-methylthymine, at an almost equal efficiency. In the LacZ reversion assay, MNNG-induced A:T to G:C as well as G:C to A:T transition mutations were efficiently suppressed by the function of mouse methyltransferase, in vivo.
Carcinogenesis 1995 Jul
PMID:Mouse methyltransferase for repair of O6-methylguanine and O4-methylthymine in DNA. 761 94

The mutational specificity of N-methylnitrosourea (MNU), nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), sodium azide (NaN3), 4-nitroquinoline oxide (4NQO), benzo[a]pyrene (BP), nitrofurantoin (NF), aflatoxin B1 (AFB1), adriamycin (ADM) and UVA-activated angelicin in Salmonella typhimurium strain TA100 has been examined using allele-specific oligonucleotide hybridization and DNA sequence analyses. These ten mutagens produced five unique classes of reversion spectra, distinct from spontaneous, or the previously characterized 5-azacytidine, ultraviolet light (UV), 8-methoxypsoralen plus UVA (PUVA) and 60Co-induced mutation spectra. For example, 90% of MNU and MNNG-induced mutations in strain TA100 revertants were G:C-->A:T transitions with the majority (82%) occurring in the first position of the CCC codon. In contrast, NaN3 preferentially induced G:C-->A:T transitions at the second codon position (78%). Although MMS, NQO, BP, NF, ADM and AFB1 induced primarily G:C-->T:A transversions (73-86%), these mutagens fall into two classes based on site preference: NF and AFB1 yielded almost exclusively position two transversions (69-78%) whereas ADM, NQO, BP and MMS exhibited a two-fold preference for site 2 over site 1 (on average 52% versus 22%). Angelicin photomutagenesis resulted in the recovery of G:C-->A:T and G:C-->T:A mutations at both codon positions in roughly equal proportions (approximately 20-25% each). Approximately 1% of the mutagen-induced revertants occurred via extragenic tRNA suppressor mutations, while 1% were multiple (usually tandem double) base substitutions. Ultraviolet mutagenesis experiments demonstrated that tandem base substitutions are promoted by pKM101-encoded mucAB gene products. A comparison of the mutagenic specificity derived for several carcinogens in hisG46 with the responses of several eukaryotic gene targets (e.g. HPRT, aprt, supF) revealed a high concordance between these targets. Thus, the Salmonella hisG46 locus provides a rapid, simple system for determining base substitution specificity and for studying mechanisms of mutagenesis.
Carcinogenesis 1994 Jan
PMID:Salmonella typhimurium strain TA100 differentiates several classes of carcinogens and mutagens by base substitution specificity. 829 52

We have studied the penetration of a labeled gastric carcinogen, N-(3H)methyl-N'-nitro-N-nitrosoguanidine (3H-MNNG), from the gastric lumen to proliferative cells in the gastric mucosa of Wistar rats. 3H-MNNG was dissolved in deionized water or dimethyl sulfoxide (DMSO) and given intragastrically through a tube in the forestomach. Cells in the S-phase were labeled by incorporation of bromodeoxy-uridine. Penetration of the carcinogen was evaluated by light microscopy after immunohistochemistry and autoradiography. Cells in S-phase labeled with 3H-MNNG (double-labeled cells) are considered to represent the cell population at risk of MNNG-induced carcinogenesis. When deionized water was used as solvent for the carcinogen, the average percentage of double-labeled cells in the pylorus was 12.0, 22.4 and 32.5 respectively, after 10, 30 and 60 min of mucosal exposure to 3H-MNNG. The corresponding percentages for the fundus mucosa were 1.7, 3.1 and 3.4, which are significantly lower than the pylorus values. When DMSO was used as solvent for the carcinogen, the percentage of double-labeled cells was 0.3 and 1.1 in the pylorus and 0.1 and 1.3 in the fundus after 10 and 30 min exposure to 3H-MNNG. Dimethyl sulfoxide caused superficial mucosal damage to the gastric mucosa and increased secretion of fluid into the stomach. Our results strongly suggest that gastric cancer develops in the pylorus because the carcinogen penetrates more easily into pyloric than fundic mucosa. The results support the view that delayed gastric emptying is a risk factor in gastric carcinogenesis, and show that DMSO counteracts the penetration of MNNG into the mucosa.
Carcinogenesis 1993 May
PMID:Penetration of N-methyl-N'-nitro-N-nitrosoguanidine to proliferative cells in gastric mucosa of rats is different in pylorus and fundus and depends on exposure time and solvent. 850 82


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