Biomedical subjects

M Tatematsu

Publications and source records attributed to M Tatematsu.

At least 55 records · Page 3Linked to original sources

PubMed2000

Clinicopathologic significance of sialyl Le(x) expression in advanced gastric carcinoma.

Sialyl Lewis(x)antigen (SLX) is a carbohydrate antigen that serves as a ligand for selectin, an adhesion molecule expressed on vascular endothelial cells. The expression of SLX in 245 patients with advanced gastric carcinoma was examined immunohistochemically, and its clinicopathologic significance was analysed. We classified the patients with advanced gastric carcinoma into 91 with differentiated type and 154 with undifferentiated type. SLX expressed in 135 of 245 patients (55%), comprising 68 (75%) patients with differentiated carcinoma and 67 (44%) with undifferentiated carcinoma. The positive rate for SLX expression was significantly higher among patients with differentiated carcinoma than among those in undifferentiated carcinoma (P<0.0001). With differentiated carcinoma, the incidence of lymph node metastasis, advanced tumour stage (stage III and IV) and liver recurrence was significantly higher in SLX-positive patients than in SLX-negative ones (P<0.0001, P = 0.0065 and P = 0. 028, respectively). Moreover, the prognoses were better in patients with SLX-negative tumours than in those with SLX-positive tumours (P = 0.019). With undifferentiated carcinoma, there were no significant correlations between SLX expression and any clinicopathological features or prognoses. The clinicopathologic significance of SLX expression in gastric carcinoma patients depends on histologic type. SLX expression may be of great relevance in predicting liver metastases in patients with differentiated carcinoma.

Aged↗

PubMed2000

p53 knockout mice (-/-) are more susceptible than (+/-) or (+/+) mice to N-methyl-N-nitrosourea stomach carcinogenesis.

Mutations of the p53 tumor suppressor gene constitute one of the most frequent molecular changes in a wide variety of human cancers. Mice deficient in p53 have recently attracted attention for their potential to identify chemical genotoxins. In this study we have investigated the susceptibility of p53 nullizygote (-/-), heterozygote (+/-) and wild-type (+/+) mice to N:-methyl-N:-nitrosourea (MNU) gastric carcinogenesis. p53 knockout mice were treated with 30 p.p.m. MNU in the drinking water 1 week on and 1 week off and killed after 5 weeks. The numbers of pepsinogen-altered pyloric glands (PAPG), putative preneoplastic lesions, were 1.8, 1.7 and 22.6 in p53 (+/+), (+/-) and (-/-) mice, respectively. In a 15 week experiment, adenomas were found in 0 of 19 (+/+) (0%), 2 of 21 (+/-) (9.5%) and 6 of 10 (-/-) (60.0%) animals. Also, one well-differentiated adenocarcinoma was observed in a p53 (-/-) mouse. After 40 weeks treatment with 120 or 30 p.p.m. MNU there was no significant difference in the incidence of gastric tumors between p53 (+/+) and (+/-) mice. However, mortality from carcinogen-induced lymphomas, leukemias and sarcomas was very much greater in the latter group. Homozygous knockout animals could not be maintained long term. PCR-single strand conformation polymorphism analysis of exons 5-8 of the p53 gene of DNA extracts from 68 gastric tumors consisting of 16 and 20 30 p.p.m. MNU-treated p53 (+/+) and (+/-) mice and 14 and 18 120 p.p.m. MNU-treated p53 (+/+) and (+/-) mice demonstrated no mutations. These results suggest that p53 may not be a direct target of MNU but rather play an important role as a gatekeeper in mouse stomach carcinogenesis induced by this direct acting agent.

Animals↗

PubMed2000

Isolation of differentiated squamous and undifferentiated spindle carcinoma cell lines with differing metastatic potential from a 4-nitroquinoline N-Oxide-induced tongue carcinoma in a F344 rat.

One differentiated squamous cell carcinoma (SCC) cell line (RSC3-E2) and two undifferentiated tumor cell lines (RSC3-LM and RSC3-E2R) with different metastatic potential were established from a 4-nitroquinoline N-oxide (4NQO)-induced differentiated SCC in F344 rat tongue. The RSC3-E2 subline was isolated from a parental cell line (RSC3-P) by single cell cloning in vitro, whereas the RSC3-LM subline was isolated from a lung metastatic focus after subcutaneous (s.c.) injection of RSC3-P cells. The RSC3-E2R cell line was isolated from a lung metastatic focus following s.c. injection of RSC3-E2 cells after X-irradiation in vitro. The RSC3-E2 cell line is keratin-positive and grows as a keratinizing tumor in nude mice, whereas RSC3-LM and RSC3-E2R cells are keratin-negative, vimentin-positive and form undifferentiated tumors. When s.c. injected into nude mice, the RSC3-E2 cell line proved to be non-metastatic, while the RSC3-LM cell line was metastatic by both hematogenous and lymphogenous routes, and the RSC3-E2R cell line was metastatic only hematogenously. In vitro relative growth rates and in vitro invasion activity of these cell lines were in the order RSC3-LM > RSC3-E2R > RSC3-E2. Chromosome analysis revealed two peaks with modal chromosome numbers of 83 and 78 for RSC3-P cells and single peaks at 83, 78 and 56 for RSC3-LM, RSC3-E2 and RSC3-E2R cell lines, respectively. Common structural abnormalities on chromosome 11 were shared by all cell lines. Mutation analysis of the p53 gene using a yeast functional assay demonstrated RSC3-LM cell line to have a point mutation at codon 269, whereas RSC3-E2 and RSC3-E2R had double mutations at codons 106 and 170 on each allele. These results suggest that the two undifferentiated RSC3-LM and RSC3-E2R tumor cell lines with different metastatic potential were generated from differentiated SCC cells via different genetic pathways as a consequence of tumor progression in vivo and in vitro, respectively. These cell lines should provide a useful model for understanding mechanisms of hematogenous and lymphogenous metastasis, as well as tumor progression of oral SCCs.

4-Nitroquinoline-1-oxide↗

PubMed2000

Mouse strain susceptibility to diethylnitrosamine induced hepatocarcinogenesis is cell autonomous whereas sex-susceptibility Is due to the micro-environment: analysis with C3H <--> BALB / c sexually chimeric mice.

In man, liver cancer is on the increase, especially in males. Sex differences also exist in rodent models. To elucidate the mechanisms, chimeric mice were produced by amalgamation of early embryos from high and low hepatocarcinogen-susceptible strains, C3H and BALB / c. Tumor formation was initiated with 10 mg / kg of diethylnitrosamine at the ages of 7 and 14 days and mice were sacrificed at 30 and 45 weeks. The chimeras were classified into XY <--> XY, XY <--> XX, XX <--> XY, and XX <--> XX in terms of sex chromosomes by means of polymerase chain reaction-simple sequence length polymorphism analysis (SSLP) using Y chromosome-specific Sry primers in combination with the D3Mit21 marker. Liver lesions were analyzed histopathologically, by immunostaining using a C3H strain-specific antibody and by DNA in situ hybridization with the Y chromosome-specific digoxigenin-labeled Y353 / B probe. Sex and strain genotyping by SSLP analysis matched histological observations, confirming the reliability of our system. The strain differences in liver tumor numbers of each strain type in XY <--> XY and XX <--> XX subtypes of C3H <--> BALB / c chimeras were retained well (P < 0. 0001 and P < 0.001, respectively), indicating a minimum influence of the C3H or BALB / c surrounding milieu on development of individual lesions. On the other hand, significant promotion of XX cell tumors was evident in phenotypically male sexually chimeric XY <--> XX and XX <--> XY chimeras for both C3H (P < 0.02) and BALB / c (P < 0.01) lesions compared to the XX <--> XX case. The results suggest the presence of hormonal or micro-environmental factors specific for males, which are not caused cell-autonomously. Basic strain differences, however, are determined by intrinsic genetic factors rather than the strain-dependent micro-environment.

Animals↗

PubMed2000

More frequent beta-catenin gene mutations in adenomas than in aberrant crypt foci or adenocarcinomas in the large intestines of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-treated rats.

Alteration of adenomatous polyposis coli (APC) is known to be an early event in neoplasia, causing activation of the beta-catenin / Tcf pathway. Although it is thought that alterations in APC and beta- catenin may complement one another, the contribution of beta-catenin mutations to colorectal carcinogenesis remains unclear. We therefore performed PCR-single strand conformation polymorphism analysis and direct sequencing of exon 3 of beta-catenin gene in adenomas, adenocarcinomas, and aberrant crypt foci (ACF), considered to be putative precursor lesions of colorectal neoplasias, in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) treated F344 rats. beta-Catenin mutations were identified in all of 7 adenomas (100%) and 6 of 12 (50%) adenocarcinomas. All of the mutations were found in codons 32 through 34, the serine encoded by codon 33 being an important phosphorylation site by glycogen synthase kinase-3beta. Regarding ACF, 14 of 46 (30.4%) were found to be mutated, eleven (78%) in codon 34, and the others in codon 45 (frequently altered in human colon cancer), and codons 47 and 56 (which have not been previously reported). The frequency of beta-catenin mutations in adenomas was significantly higher than in ACF (P < 0.001) and adenocarcinomas (P < 0.05). Thus, beta-catenin mutations may have more importance in the genesis of adenomas than ACF or adenocarcinomas in rat colon carcinogens by PhIP.

Adenocarcinoma↗

PubMed2000

[Eradication model employing Mongolian gerbils treated with chemical carcinogen and infected with Helicobacter pylori--implications for human cancer prevention].

To explore the 'causal link' between Helicobacter pylori(Hp) infection and stomach carcinogenesis, we have established experimental models of stomach carcinogenesis in Mongolian Gerbils(MGs) using the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and N-methyl-N-nitrosourea(MNU). The incidence of adenocarcinoma was significantly higher in animals treated with Hp than in the controls. Eradication of Hp was effective in reducing the incidence of adenocarcinoma. No gastric carcinoma was found without any chemical carcinogen. Hp infection enhances glandular stomach carcinogenesis not only of well-differentiated type but also poorly differentiated type and signet ring cell type. Eradication of Hp, apparently a gastric promoter rather than gastric carcinogen, may be useful as a measure for prevention of stomach cancer.

Adenocarcinoma↗

PubMed1999

A novel glycosyltransferase with a polyglutamine repeat; a new candidate for GD1alpha synthase (ST6GalNAc V)(1).

The fifth type GalNAcalpha2,6-sialyltransferase (mST6GalNAc V) was cloned from a mouse brain cDNA library. mST6GalNAc V exhibited type II transmembrane topology containing a polyglutamine repeat, which showed 42.6% and 44.8% identity to mouse ST6GalNAc III and IV, respectively. Northern blot analysis revealed that the mST6GalNAc V gene was specifically expressed in forebrain and cerebellum. mST6GalNAc V exhibited GD1alpha synthetic activity from GM1b the same as mST6GalNAc III and IV. The activity ratio of GM1b toward fetuin and the expression pattern were completely different among the three ST6GalNAcs. Interestingly, the polyglutamine repeat number was different from that of inbred mice. We report the first glycosyltransferase with a polymorphic polyglutamine repeat.

Amino Acid Sequence↗

PubMed1999

Biological differences between reflux stimulated proliferative stomal lesions and N-methyl-N'-nitro-N-nitrosoguanidine induced carcinomas in Wistar rats.

The morphology and evolution of epithelial lesions that developed at a gastrojejunal stoma due to reflux of duodenal contents were compared with MNNG-induced carcinomas in the pyloric mucosa of rats in a long term experiment. Random bred male Wistar rats were given MNNG in drinking water (100 mg/l) for 12 weeks and then one group was submitted to a gastrojejunal anastomosis at the greater curvature in the oxyntic mucosa. Untreated rats underwent either gastrojejunostomy or gastrotomy. The animals were killed at the 24th and 66th weeks of the experiment. The lesions obtained in the pyloric mucosa and in the mucosa of the gastrojejunal stoma were analyzed histologically using hematoxylin and eosin staining and immunohistochemistry for pepsinogen isoenzyme 1. Duodenal reflux induced proliferative lesions at the gastrojejunal junction that increased in incidence and size with time. Histologically they consisted of benign epithelial proliferation of gastric type. No evidence of malignant transformation within the gastric components of the proliferative lesions at the gastrojejunal stoma was observed even at the 66th week. Adenocarcinomas induced by MNNG in the pyloric mucosa increased in size during the experiment and were morphologically and histochemically distinct from the proliferative lesions at the gastrojejunal junction. In conclusion, proliferative lesions at the gastrojejunal stoma stimulated by duodenal reflux are biologically distinct from adenocarcinomas induced by MNNG in the pyloric mucosa. They do not seem to be precursor lesions of gastric carcinogenesis, as they do not undergo malignant transformation even after long-term, up to 66 weeks, follow-up.

Adenocarcinoma↗

PubMed1999

Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell.

The chemosensitivity of the sequence of steps responsible for metastasis formation including circulating tumor cells and micrometastases to a 5-fluorouracil derivative (UFT) was examined with a novel micrometastasis model featuring Lewis lung carcinoma cells tagged with the bacterial LacZ gene and hygromycinR gene (hygR). Metastases in the lung could be specifically detected at the single-cell level by X-Gal staining after inoculation of LacZ-transfected tumor cells. Spontaneous metastasis in mice bearing subcutaneous primary tumors was significantly inhibited by UFT at doses of 15-20 mg/kg when it was orally administered from day 14, during the early stage of micrometastasis formation, but not by late administration from day 22. Experimental pulmonary metastasis was also inhibited without significant toxic side effects by oral administration of UFT at a daily dose of 20 mg/kg from day 4, when the tumor cells start new growth in the lung, but not by daily treatment from 8 days after intravenous injection. Oral administration of UFT had no effect on tumor cell arrest in the lung as detected by X-Gal staining. Furthermore, PCR analysis revealed that circulating tumor cells in the peripheral blood of mice bearing primary tumors after subcutaneous injection of hygR-tagged tumor cells were significantly reduced by the oral administration of UFT for 7 days in a dose-dependent manner. These results indicate that circulating tumor cells in the peripheral blood and micrometastases in the initial growth phase in the lungs are sensitive to this chemotherapeutic agent, and suggest that micrometastasis formation can be effectively inhibited by long-term oral administration of anticancer agents with minimal toxic side effects.

Administration, Oral↗

PubMed1999

Effects of low dose catechol on glandular stomach carcinogenesis in BALB/c mice initiated with N-methyl-N-nitrosourea.

The effects of low dose catechol administration in the diet on stomach carcinogenesis in mice after initiation with N-methyl-N-nitrosourea (MNU) in the drinking water were investigated. Male, 6-week-old, BALB/c mice were given MNU in the drinking water intermittently for 1-week periods at 1-week intervals for a total of 3 weeks at a concentration of 120 ppm (groups 1 and 3). Groups 2 and 4 served as non-initiated controls. From week 7, groups 1 and 3 were divided into four subgroups and the mice were fed on a diet containing 4 ppm (groups la and 3a), 20 ppm (groups 1b and 3b), 100 ppm (groups 1c and 3c), 500 ppm (groups 1d and 3d) or 0 ppm (groups 2 and 4) catechol for 44 weeks. At week 50, appreciably enhanced development of pepsinogen 1 altered pyloric glands (PAPG) was noted in groups 1c and 1d. The incidences of adenomatous hyperplasia and carcinomas were not affected in any of the catechol-treated groups as compared with corresponding controls on a basal diet. Thus, the administration of catechol in the diet at low doses enhanced only preneoplastic lesion development and not neoplastic lesion development. From these results, we conclude that the biological significance of the catechol promoting effect at probable human exposure levels on gastric cancer is probably limited, while the PAPG may be a sensitive endpoint lesion for mouse glandular stomach carcinogenesis.

Adenocarcinoma↗

PubMed1999

Strong expression of glutathione S-transferase placental form in early preneoplastic lesions and decrease with progression in hamster buccal pouch carcinogenesis.

The objective of this work was to investigate the expression of glutathione S-transferase placental form (GST-P) in 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Lesions were classified histopathologically into four categories, simple hyperplasia, papillary and nodular (PN) hyperplasia, papilloma and squamous cell carcinoma (SCC). Respective mean percentage GST-P positive areas were 81.6 +/- 7.3%, 76.1 +/- 7.3%, 25.8 +/- 4.9% and 1.9 +/- 1.2%, with significant (P < 0.001) differences confirmed between each of the lesions. These results indicate that GST-P is a useful positive marker for neoplastic lesions and that a decreased expression occurs with progression so that it may be predictive of future development of malignancy.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Promotional effects of CO2 laser on DMBA-induced hamster buccal pouch carcinogenesis as shown by immunohistochemistry of the placental form of glutathione S-transferase.

BACKGROUND AND OBJECTIVE: The purpose of the present study was to investigate the kinetics of the expression of the placental form of glutathione S-transferase (GST-P), a useful marker of premalignant lesions, and cell proliferation after CO2 laser surgery on the carcinogen-initiated epithelium. STUDY DESIGN/MATERIALS AND METHODS: CO2 laser incisions were made on buccal pouch epithelium of 36 hamsters after initiation by 9,10-dimethyl-1,2-benzanthracene (DMBA) (group 1, G1), and scalpel incisions were similarly made on 33 animals (group 2, G2). Twenty animals not treated further after initiation were used as DMBA-treated controls. Incidence of malignant transformation, expression of GST-P, and cell proliferation were examined. RESULTS: The incidence of malignant transformation in G1 and G2 increased significantly (G1: P < 0.001; G2: P < 0.05) compared with that in DMBA-treated controls. GST-P expression of hyperplasia in G1 and G2 decreased significantly (P < 0.001) compared with that in DMBA-treated controls. In hyperplasia, cell proliferation of the GST-P-negative area was significantly (P < 0.001) higher than that of the GST-P-positive area. CONCLUSION: The incisions, particularly by the CO2 laser, on the initiated areas made expression of GST-P decrease and cell proliferation increase in the GST-P-negative areas. These incisions may serve to promote malignant transformation.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Rare mutations of p53, Ki-ras, and beta-catenin genes and absence of K-sam and c-erbB-2 amplification in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat stomach cancers.

Rat stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) have been widely used as a model for human stomach cancers of the differentiated type. However, there has been little information regarding their molecular basis. In this study, we examined the genetic alterations reported in human stomach cancers in 10 rat stomach cancers that had been induced in male ACI/N rats by administering MNNG in the drinking water. One of the 10 cancers had a mutation of the p53 gene at the second position of codon 171 (Val --> Glu). However, none of the 10 cancers had mutations in codons 12, 13, or 61 of Ki-ras or in the N-terminal phosphorylation sites of the beta-catenin gene. Southern blot analysis showed no amplification of K-sam or c-erbB-2 in the seven cancers examined. Finally, we searched for microsatellite alterations in 12 loci in nine cancers, but no alterations were observed. As these genetic alterations are observed in only a minor fraction of human stomach cancers, further analysis of genetic and epigenetic alterations in MNNG-induced rat stomach cancers is needed to disclose the major mechanisms of stomach carcinogenesis.

Animals↗

PubMed1999

Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies.

Free cancer cells exfoliated from cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in patients with gastric and ovarian cancers. This study was designed to evaluate the prognostic significance of free cancer cells in peritoneal washes detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for the carcinoembryonic antigen (CEA) gene was found to be more sensitive than cytology for detection of free tumor cells in the peritoneal washes, collected at laparotomy from 199 gastric carcinoma patients, with higher detection rates for each of the T-categories in the TNM classification. Six patients with synchronous and 5 with recurrent peritoneal dissemination were found among 25 advanced cancer patients with positive PCR and negative cytology results. Positive PCR results were significantly associated with poor survival of curatively resected advanced gastric carcinoma patients (P < 0.001). A rapid method for detecting CEA mRNA using the LightCycler and the dsDNA binding dye SYBR green I was also developed. The results obtained using this technique were essentially the same as those obtained using the conventional RT-PCR method. Furthermore, RT-PCR analysis with primers specific for MUC1 epithelial mucin were performed on peritoneal washes from patients with ovarian cancer. Peritoneal washes from 21 of 25 ovarian carcinoma patients, including all 17 with positive cytology results, were positive for MUC1 mRNA, again indicating a higher sensitivity using this method than conventional cytology. Highly sensitive and rapid detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is a powerful technique to predict peritoneal dissemination in patients with gastric and ovarian cancers.

Animals↗

PubMed1999

Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5-fluorouracil.

Antimetastatic effects of 5-FU and its derivative, 1-hexylcarbamoyl-5-fluorouracil (HCFU) on human gastric cancer micrometastasis and their mode of action were evaluated, using a spontaneous lung metastasis model (HY-1) in nude mice. Metastases were first detected in the lung from 4 weeks after subcutaneous transplantation, growing intravascularly and forming micrometastases at 100% incidence by 6 weeks after implantation. Lung metastasis in mice bearing subcutaneous tumors was significantly inhibited by HCFU at doses of 100-150 mg kg(-1) day(-1) without severe toxic side-effects, when orally administered three times per week either from week 4 or week 6 to 9 weeks after implantation. Spontaneous lung metastasis was also inhibited by the administration of 5-FU, but to lesser extent than with HCFU at equimolar low doses. Apoptosis within primary tumors and lung metastatic foci, as detected by the terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling method, was found to be significantly enhanced by HCFU as well as 5-FU administration at doses of more than 100 mg kg(-1) day(-1) and 50 mg kg(-1) day(-1) respectively. However, proliferating activity of the metastatic foci, as evaluated by MIB-1 immunostaining, was not significantly suppressed by HCFU or 5-FU treatment. Furthermore, polymerase chain reaction analysis using human specific primers for the beta-globin gene, which proved to be capable of detecting 10 tumor cells/ml mouse blood, revealed that circulating tumor cells in the peripheral blood of mice bearing primary tumors were reduced by HCFU or 5-FU administration. These results indicate that circulating tumor cells in blood and micrometastases in the lung are sensitive to these chemotherapeutic agents, and suggest that the anti-metastatic effect of these agents is mediated, at least in part, by enhanced apoptosis rather than by inhibition of cell proliferation.

Animals↗

PubMed1999

Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens.

Helicobacter pylori (Hp) is thought to be a stomach carcinogen from epidemiological findings. To determine the effects of infection with the bacteria on experimental carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. Male MGs were treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by inoculation with Hp or infected with Hp followed by N-methyl-N'-nitro-N-nitrosoguanidine administration. Animals were killed at week 50, and their excised stomachs underwent microbiological and histopathological examinations. In addition, a serological investigation was performed. The incidences of adenocarcinomas were significantly higher in animals treated with 60 or 300 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 10 weeks followed by Hp inoculation or Hp followed by 20 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 30 weeks than in the respective controls. Moreover, tumour-bearing animals had higher titres of anti-Hp antibodies than tumour-free animals. Of interest was the finding that a dose of 100 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine given to infected gerbils eradicated the Hp in about half the animals, with a concomitant reduction in the promoting effect. No tumours were found in animals infected with Hp without N-methyl-N'-nitro-N-nitrosoguanidine or non-treated gerbils. Hp infection enhances glandular stomach carcinogenesis in MGs treated with N-methyl-N'-nitro-N-nitrosoguanidine. Animals with high titres of anti-Hp antibodies are at greatest risk of developing neoplasms.

Adenocarcinoma↗

PubMed1999

Development and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced aberrant crypt foci in the rat large intestine.

Aberrant crypt foci (ACF) are generally considered to be preneoplastic lesions for colon cancer. To assess their induction by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a colon carcinogen, we performed a sequential study of ACF morphology and localization. F344 male rats were given PhIP, and methylene blue-stained colon epithelium and isolated crypts were analyzed at weeks 12, 25, 50, and 75. Each crypt was classified into 2 groups, "single" with round bottoms and "bifurcating" displaying V-shaped clefts (indicating proliferation). In combination with the number of crypts in an ACF, this classification was a good indicator for the generation of ACF in line with the fission mechanism of growth. Increasing numbers of crypts in ACF through weeks 12 to 75 and decreased percentages of ACF with bifurcating crypts at the late time points indicated that proliferation of crypts occurs predominantly during the early stages. The distribution pattern showed a significant shift (P < 0.000005) from the distal to the proximal part of the large intestine between weeks 25 and 50. Adenocarcinomas were first found to develop at week 50 in the ascending colon and cecum where bifurcating crypts were generally lacking at weeks 12 and 25. These data suggest the existence of (1) proliferating ACF which contains bifurcating crypt(s) and (2) quiescent or senescent ACF which consists of only single crypts.

Animals↗

PubMed1999

Clonality of urogenital organs as determined by analysis of chimeric mice.

Though the first mammalian chimera was reported in 1961, suitable markers for different animal strains which are easily detectable in histological sections of all or most organs have not existed. Chimeric mice were produced having an excellent histological marker, the C3H antigen, which is strain-specific and fulfills all the criteria for an ideal strain-specific histological marker. Using male and female C3H-Balb/c chimeric mice we examined epithelial cells of urogenital organs and their morphological or functional units, such as the glomerulus, to determine whether individual organs and their morphological subunits were monoclonal or polyclonal in origin. We found that the epithelial parenchyma of most male and female urogenital organs (the prostate, seminal vesicle, epididymis, ovaries, vagina, kidney, ureter and bladder) and their morphological subdivisions were derived from cells of both input strains, indicating a polyclonal origin for each organ and/or organ component. A notable exception was the uterus in which all individual uterine glands examined (n = 403) were found to be either entirely Balb/c or entirely C3H, indicating a monoclonal origin. The clonality of urogenital structures is discussed in terms of the morphogenesis of the urogenital system.

Animals↗