<i>N</i>‐Methyl‐<i>N</i>‐nitrosourea Concentration‐dependent, Rather than Total Intake‐dependent, Induction of Adenocarcinomas in the Glandular Stomach of BALB/c Mice

Yamachika, Takasuke; Nakanishi, Hayao; Inada, Ken Ichi; Tsukamoto, Tetsuya; Shimizu, Nobuyuki; Kobayashi, Kiyoshi; Fukushima, Shoji; Tatematsu, Masae

doi:10.1111/j.1349-7006.1998.tb00575.x

Cited by 47 publications

(46 citation statements)

References 26 publications

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“…Thus milder treatment schedules were selected here. We earlier reported that the proportion of undifferentiated adenocarcinomas in the glandular stomach induced by MNU depends on the concentration of the carcinogen 22 and in this study, all adenocarcinomas were of well-differentiated type.…”

Section: Discussionsupporting

confidence: 67%

Gastric Carcinogenesis and Intestinalization Induced by N-methyl-N-nitrosourea in the Senescence-Accelerated Mouse(SAMP3).

et al. 2003

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Abstract:The relationship between gastric neoplasia and intestinal metaplasia, a process whose incidence increases with age, remains controversial. In the present experiment, we therefore investigated induction of both intestinal metaplasia and gastric cancers in the Senescence-accelerated mouse (SAMP3/Aicc) treated with N-methyl-N-nitrosourea (MNU). Seven-week-old animals of both sexes received the carcinogen in their drinking water at 120 or 60 ppm on alternative weeks for 10 weeks, or continuously at 30 ppm for the same period, then maintained without further treatment until sacrificed at week 50. The incidences of adenocarcinomas in the 120, 60, and 30 ppm MNU treated and control groups were 6/10 (60%), 5/16 (31.3%), 1/17 (5.9%), and 0/6 (0%) in males, and 2/7 (28.6%), 3/13 (23.1%), 1/6 (16.7%), and 0/9 (0%) in females, respectively. All neoplasms were of well-differentiated type, mainly consisting of gastric epithelial type cells. With immuno-and enzyme-histochemistry, intestinal alkaline phosphatase (I-ALP) positive intestinal absorptive cell-like elements were observed in regions of hyperplasia, adenomas, and adenocarcinomas of MNU treated mice, but no phenotypic expression of goblet or Paneth cells was found. In the control mice, gastric mucosa showed no intestinal epithelium phenotype. Since the degree of appearance of I-ALP positive cells in the lesions in SAMP3/Aicc mice was not different from that found for six other strains mice in our previous work, the results suggest that Senescence-acceleration may not influence intestinalization in the gastric mucosa or induction of gastric carcinomas. (J Toxicol Pathol 2003; 16: 33-39)

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Section: Discussionsupporting

confidence: 67%

Gastric Carcinogenesis and Intestinalization Induced by N-methyl-N-nitrosourea in the Senescence-Accelerated Mouse(SAMP3).

et al. 2003

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“…MNU (Sigma Chemical) was dissolved in distilled water at a concentration of 240 ppm and was freshly prepared twice per week for administration in drinking water in light-shielded bottles. The 6-week-old wild-type and Jnk1 À/À mice were given drinking water containing 240 ppm of MNU on alternate weeks for a total of 5 weeks of exposure, according to a protocol described in a previous report (19). The MNU-treated mice were sacrificed at 40 weeks after starting MNU administration.…”

Section: Methodsmentioning

confidence: 99%

c-Jun NH2-Terminal Kinase 1 Is a Critical Regulator for the Development of Gastric Cancer in Mice

et al. 2008

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c-Jun NH 2 -terminal kinase (JNK) links several cellular processes, including proliferation and survival, and is believed to be involved in carcinogenesis. However, the role of JNK in gastric tumorigenesis is unknown. Immunohistochemical analysis reveals that JNK is frequently activated in human gastric cancer tissue. We investigated whether JNK1, a major JNK isozyme, is involved in chemically induced gastric cancer development. Mice lacking JNK1 exhibited a marked decrease in gastric carcinogenesis induced by N-methyl-N-nitrosourea, relative to their wild-type counterparts. Impaired tumor development correlated with decreased tumor initiation, which is associated with the production of reactive oxygen species. We also found that lower levels of tumorigenesis were correlated with the decreased expression of cyclin D and CDK as well as decreased cell proliferation. Taken together, JNK seems to be involved in both tumor initiation and promotion and may be an attractive target for the prevention of gastric carcinogenesis. [Cancer Res 2008;68(13):5031-9]

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“…Sixty-five PPARg (+/À) and 42 wild-type (+/+) mice, all male, age 4 to 7 weeks, were randomly divided into four groups, respectively. Animals in groups 2, 3, 6, and 7 were given drinking water containing 240 ppm MNU in light-shielded bottles on alternate weeks for a total of 10 weeks exposure, according to the protocol described in a previous report (37). Animals in groups 1, 4, 5, and 8 received only water.…”

Section: Methodsmentioning

confidence: 99%

Chemopreventive Effect of Peroxisome Proliferator–Activated Receptor γ on Gastric Carcinogenesis in Mice

Lü¹,

Imamura²,

Nomura³

et al. 2005

Cancer Research

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Peroxisome proliferator-activated receptor ; (PPAR;) is known to be expressed in several cancers, and the treatment of these cancer cells with PPAR; ligands often induces cell differentiation and apoptosis. Recently, the chemopreventive potential of PPAR; ligands on colon carcinogenesis was reported, although the effect of PPAR; on colon carcinogenesis and the mechanism of the effect remain controversial. In this study, we attempted to elucidate the role of PPAR; in gastric carcinogenesis and explored the possible use of PPAR; ligand as a chemopreventive agent for gastric cancer. N-methyl-N-nitrosourea (MNU, 240 ppm) was given in drinking water for 10 weeks to induce gastric cancer in PPAR; wild-type (+ +/+ +) and heterozygous-deficient (+ +/À À) mice, followed by treatment with PPAR; ligand [troglitazone, 0.15% (w/w) in powder food] or the vehicle alone for 42 weeks. At the end of the experiment, PPAR; (+ +/À À) mice were more susceptible to MNU-induced gastric cancer than wild-type (+ +/+ +) mice (89.5%/55.5%), and troglitazone significantly reduced the incidence of gastric cancer in PPAR; (+ +/+ +) mice (treatment 55.5%/vehicle 9%) but not in PPAR; (+ +/À À) mice. The present study showed that (a) PPAR; suppresses gastric carcinogenesis, (b) the PPAR; ligand troglitazone is a potential chemopreventive agent for gastric carcinogenesis, and (c) troglitazone's chemopreventative effect is dependent on PPAR;. (Cancer Res 2005; 65(11): 4769-74)

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N‐Methyl‐N‐nitrosourea Concentration‐dependent, Rather than Total Intake‐dependent, Induction of Adenocarcinomas in the Glandular Stomach of BALB/c Mice

Cited by 47 publications

References 26 publications

Gastric Carcinogenesis and Intestinalization Induced by N-methyl-N-nitrosourea in the Senescence-Accelerated Mouse(SAMP3).

Gastric Carcinogenesis and Intestinalization Induced by N-methyl-N-nitrosourea in the Senescence-Accelerated Mouse(SAMP3).

c-Jun NH2-Terminal Kinase 1 Is a Critical Regulator for the Development of Gastric Cancer in Mice

Chemopreventive Effect of Peroxisome Proliferator–Activated Receptor γ on Gastric Carcinogenesis in Mice

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