Cooperative programme on short-term assays for carcinogenicity in Japan.
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Bacillus subtilis↗
Biomedical subjects
T Kawachi
Publications and source records attributed to T Kawachi.
Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas.
Intestinal metaplasia of the human stomach was classified into two types, complete and incomplete. The complete type was associated with the intestinal marker enzymes sucrose alpha-D-glucohydrolase, alpha, alpha-trehalase, aminopeptidase (microsomal) (APM), and alkaline phosphatase (ALP). Tissue of this type contained goblet cells and Paneth's cells but not high-iron diamine (HID)-positive mucin staining with HID-Alcian blue. The incomplete type of intestinal metaplasia was associated with sucrose alpha-D-glucohydrolase, APM, goblet cells, and HID-positive mucin but not with alpha, alpha-trehalase, ALP, or Paneth's cells. For the examination of the distribution of the complete and incomplete types in 84, 27, and 16 resected specimens of human stomach with gastric carcinoma, gastric ulcer, and duodenal ulcer, respectively, disaccharidases were located with Tes-Tape. Specimens with intestinal metaplasia were divided into three classes: complete type only (class I), incomplete type only (class II), and a mixture of areas of the complete and incomplete types (class III). Of the 84 specimens from patients with gastric carcinoma, intestinal metaplasia was found in 76 (01%), and the percentages of specimens of classes I, II, and III were 32, 22, and 46, respectively. In these specimens, the percent incidence of class I increased and that of class II decreased with age. Of the 27 specimens from patients with gastric ulcer, 16 (59%) shopwed intestinal metaplasia and 10 of the 16 (63%) specimens were of class II. Of the 16 specimens from patients with duodenal ulcer, only 3 (19%) specimens showed intestinal metaplasia and all of them were of class II. The relationships of the complete and incomplete types of intestinal metaplasia to gastric carcinoma wre studied in 26 foci of minute carcinoma of the stomach less than 5 mm in largest diameter. Nineteen of 20 (05%) foci of the intestinal type of minute carcinoma were surrounded by intestinal metaplasia and 16 foci (80%) were surrounded by the incomplete type of intestinal metaplasia.
Adult↗
Induction of liver tumors in Wistar rats by sodium nitrite given in pellet diet.
Sodium nitrate was given to male noninbred Wistar rats at levels of 800 ppm and 1,600 ppm in a pellet diet for 646 experimental days. The first tum or was found on day 441 in the liver of a rat given a diet containing 800 ppm sodium nitrite. On day 646, liver tumors were found in 1 of 22 rats (4.5%) on an 800-ppm sodium nitrite diet and in 5 of 19 rats (26.3%) on a 1,600-ppm sodium nitrite diet. The incidence of liver tumors in the rats fed 1,600 ppm sodium nitrite was significantly different from that in controls as judged by the t-test (P < 0.05). A hepatocellular carcinoma and a hemangioendothelial sarcoma of the liver were found on day 646 in 2 rats fed 1,600 ppm sodium nitrite. One mammary tumor but no liver tumors were found in the 19 control rats. The concentration of sodium nitrite decreased after preparation of the pellet diet, but it was still at least 70% of the initial amount when the pellets were given to the rats. Volatile N-nitroso compounds, especially dimehylnitrosamine, at ppm levels were detected in the pellet diet with a gas chromatography-thermal energy analyzer.
Adenoma↗
Increased agglutinability of bladder cells by concanavalin A after administration of carcinogens.
The agglutination by concanavalin A of isolated epithelial cells of the rat bladder was examined after in vivo treatment of rats with various bladder carcinogens for one week. The carcinogens tested were N-butyl-N-(4-hydroxybutyl)nitrosamine, dibutylnitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, 2-acetylaminofluorene, 2-napthylamine, benzidine, N-methyl-N-nitrosourea, and cyclophosphamide, and they were given to male Wistar rats p.o., s.c., intravesically, or i.p. As negative controls, the effects of administration of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, dimethylnitrosamine, N-methyl-N'-nitro-N-nitrosoguanidine, and surgical implantation of glass beads in the bladder were also tested. One week after the start of treatment, epithelial cells were isolated from the bladder by sonication, and agglutination of the isolated cells with concanavalin A was assayed. The observed agglutinabilities of isolated cells were found to be closely correlated with the reported bladder carcinogenicities of these chemicals in rats. Thus, concanavalin A agglutination of bladder cells should be a useful rapid in vivo mammalian system for screening bladder carcinogens.
2-Acetylaminofluorene↗
Effect of simultaneous administration of leupeptin on induction of bladder tumors in rats by N-butyl-N-(4-hydroxybutyl)-nitrosamine.
Male Wistar rats were given a diet containing 0.1% leupeptin, a microbial protease inhibitor, and drinking water containing 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 8 weeks. Leupeptin did not have any detectable effect on the induction of bladder tumors by BBN in week 40, in terms of the weight of the bladder including the tumor, the number of tumors per bladder, the extent of invasion, or the incidences of hyperplasia, papilloma, and cancer. This result is in marked contrast to the previous findings that leupeptin enhanced BBN-induced bladder carcinogenesis when administered continuously after BBN-treatment.
Animals↗
Esophageal carcinoma in rats induced by N-amyl-N-methylnitrosamine.
N-Amyl-N-methylnitrosamine (AMN) induced esophageal carcinoma in Donryu strain rats when given in drinking water. The incidence of carcinomas was high when AMN was given as 0.0015% solution for 90 days or 0.003% solution for 60 days. There was no difference in the incidence in males and females. Sequential studies showed that 4-week administration was necessary to induce esophageal papillomas, and 8-week administration to induce esophageal carcinomas. Whole-body autoradiography after intravenous injection of N-amyl-N-methyl[14C]-nitrosamine (14C-AMN) indicated that AMN accumulated preferentially in the esophagus.
Age Factors↗
Chemotherapeutic study on canine gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine.
Studies were made on the chemotherapy of gastric cancer in dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Four male Beagle dogs were given a solution of ENNG at 100 approximately 150 microgram/ml with or without 0.4% Tween 60 to drink for 5 approximately 8 months. They all developed gastric adenocarcinomas, which were confirmed by histological examination of biopsy specimens taken in months 13 approximately 32 of the experiment. After confirming the presence of gastric cancer, 1-n-hexylcarbamoyl-5-fluorouracil (HCFU), a derivative of 5-fluorouracil, was given to the dogs orally as capsules at a daily dose of 5 or 10 mg/kg body weight. One dog died from adverse effects of HCFU 12 days after the beginning of chemotherapy. The other 3 dogs were treated with CHFU for 82 approximately 424 days. In these dogs, the tumor size, measured by X-ray examination, increased during chemotherapy. On autopsy, the tumors in the stomach were found to be restricted to the antrum, and metastases of the gastric adenocarcinomas to the regional lymph nodes and/or liver were found in 2 dogs. No degenerative changes of tumor cells were found in the stomach or metastasized organs, except for necrosis of cells in a perigastric regional lymph node of the dog. The value of using canine gastric cancer in studies on chemotherapy is discussed.
Adenocarcinoma↗
Intestinal metaplasia and adenocarcinoma induced in the stomach of rats by N-propyl-N'-nitro-N-nitrosoguanidine.
PNNG, the propyl derivative of MNNG, was administered to Wistar rats by a concentration of 59.5 micrograms/ml in the drinking water for 4, 8, and 12 months and the rats were killed in the 15th month. Intestinal metaplasia was induced in the glandular stomachs of 25%, 75%, and 83% of the rats treated with PNNG for 4, 8, and 12 months, respectively. Metaplastic glands were found in the pyloric region, especially near the pyloric ring. These glands contained goblet cells and columnar cells with striated borders. No tumors were found in the stomach of rats after 4-months treatment, but adenomas were found after 8-months treatment, and both adenomas and adenocarcinomas after 12-months treatment.
Adenocarcinoma↗
Promoting action of croton oil on gastrocarcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in rats.
The promoting effect of croton oil on gastrocarcinogenesis by MNNG was examined in male Wistar rats. Gastric carcinomas were found in five of 10 rats given 83 micrograms/ml MNNG for three months and then 0.02% croton oil with 0.5% Tween 60 as solvent for nine months. No gastric carcinomas were found in rats given MNNG for three months and then Tween 60 only for nine months. The incidence of gastric carcinomas in these two groups was significantly different (p less than 0.05). No tumors were found in rats given only croton oil with Tween 60.
Adenocarcinoma↗
Induction of enzyme-altered islands in rat liver by tryptophan pyrolysis products.
Two new gamma-carboline derivatives, 3-amino-1,4-dimethyl-5H pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H pyrido[4,3-b]indole (Trp-P-2), isolated from the pyrolysis products of tryptophan, were found to be potent mutagens. When weanling rats were injected with Trp-P-1 and then given diet containing phenobarbital, they developed enzyme-altered islands in the liver. Since these islands are considered to be formed by immediate progeny of "initiated cells" and cell precursors in hepatocarcinogenesis, Trp-P-1 may well be carcinogenic in rat liver.
Adenosine Triphosphatases↗
Further studies on the carcinogenicity of a food additive, AF-2, in hamsters.
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Animals↗
Purification and properties of alkaline phosphatase from the mucosa of rat small intestine.
Alkaline phosphatase [orthophosphoric monoester phosphohydrolase, EC 3.1.3.1] was purified from the mucosa of rat small intestine by butanol extraction, ethanol fractionation, gel filtration, with controlled-pore glass-10 and DEAE-cellulose column chromatography. On the gel filtration, the enzyme activity was separated into three peaks; A in the void volume, B and C at lower molecular weight positions. Enzyme A was purified to homogeneity. The activity of enzymes A, B, and C was detected even on sodium dodecyl sulfate-polyacrylamide gel electrophoresis at the position of the protein of enzyme A, which had a molecular weight of 110,000 daltons. Enzymatic properties such as pH optimum, Km value for the substrate, heat inactivation and inhibition by amino acids were the same in all three enzymes. Based on these findings, together with the elution positions on gel filtration, enzyme A was regarded as an aggregate, and enzymes B and C as dimer and monomer molecules, respectively.
Alkaline Phosphatase↗
Induction of intestinal metaplasia and carcinoma in the glandular stomach of rats by N-alkyl-N'-nitro-N-nitrosoguanidines.
Induction of intestinal metaplasia and carcinoma of the stomach in Wistar rats by four homologs of N-alkyl-N'-nitro-N-nitrosoguanidine (N-alkyl-NNG) was investigated. N-Propyl-, N-butyl, N-isobutyl, and N-pentyl-NNG's were administered to rats as 0.34mM solutions in the drinking water for 12 months and the rats were killed about 6 months later. Intestinal metaplasia was found in the glandular stomach of 100%, 50%, 44%, and 17% of the rats treated with N-propyl-, N-butyl-, N-isobutyl-, and N-pentyl-NNG's, respectively. Adenocarcinoma of the glandular stomach was found in 29% of the rats treated with N-propyl-NNG, but not in those treated with other N-alkyl-NNG's. In the control group, 11% of the rats had intestinal metaplasia but none had tumors.
Adenocarcinoma↗
Agglutination of bladder cells by concanavalin A during the early phase of treatment of rats with N-butyl-N-(4-hydroxybutyl)nitrosamine.
N-Butyl-N-(4-hydroxybutyl)nitrosamine was given to male Wistar rats at a dose of 0.05% in the drinking water for one to five weeks, and agglutination of cell isolated from their bladder by concanavalin A (Con A) was determined at intervals during and after treatment. Mucosal cells were isolated from everted bladder by ethylenediaminetetraacetate treatment and sonication. As early as one week after the start of treatment, Con A caused some agglutination of isolated bladder cells, and this agglutination increased with time, reaching an almost constant value from the third week. Con A agglutination of bladder cells induced by N-butyl-N-(4-hydroxybutyl)nitrosamine treatment for only one week appeared to be irreversible, and it was still observed two weeks after the end of treatment. Scanning electron microscopy showed that microvilli developed on the luminal surface of mucosal cells in situ at the time when the isolated cells became agglutinable with Con A. Measurement of agglutinability of isolated bladder cells with Con A might be a useful way of detecting very early changes in bladder carcinogenesis.
Agglutination↗
Quantitative measurement of intestinal marker enzymes in intestinal metaplasia from human stomach with cancer.
Intestinal metaplasia in human stomach was distinguished macroscopically into sucrase-positive and trehalase-positive areas, and sucrase-positive and trehalase-negative areas, by location of these disaccharidase activities with TES-Tape. After location of these two areas with TES-Tape, tissues were taken from them for colorimetric measurement of sucrase, trehalase, leucine aminopeptidase (LAP), and alkaline phosphatase (ALP). Results showed that in the mucosa from sucrase-positive and trehalase-negative areas, trehalase activity was not detectable and the activities of sucrase, LAP, and ALP were lower than in sucrase-positive and trehalase-positive areas.
Alkaline Phosphatase↗
Concanavalin A agglutination of bladder cells of rats treated with bladder carcinogens; a rapid new test to detect bladder carcinogens.
N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), which is a potent, specific bladder carcinogen in rats, and its related compounds were orally administered to rats for 1 week. The bladder cells were isolated by the treatment with EDTA and sonication and they were subjected to agglutination assay by concanavalin A (Con A). Bladder cells obtained from rats treated with BBN, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) and N-butyl-N-(2-hydroxyethyl)nitrosamine (BHEN) were agglutination-positive, while those cells treated with N-tert-butyl-N-(4-hydroxybutyl)-nitrosamine (t-BBH) and N-butyl-N-(3-hydroxypropyl)nitrosamine (BHPN) were negative. Results obtained by this method were highly correlated with the known carcinogenicity of BBN and its analogues. Therefore, this method could be used for rapid screening of bladder carcinogens.
Animals↗
Induction of intestinal metaplasia in the stomachs of rats by N-methyl-N'-nitro-N-nitrosoguanidine.
N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered orally to male Wistar rats at a concentration of 83 microgram/ml in the drinking water for 2, 4, 5, and 7 months; the rats were killed at about month 15. Intestinal metaplasia was found in the stomachs of 80-100% of the rats treated with MNNG for 4 or more months, of 37.5% treated with MNNG for 2 months, and of 10% of the controls. Metaplastic glands, composed of goblet cells and columnar cells with striated borders, were found in the pyloric region. Paneth's cells were found at the bottom of metaplastic glands in a rat treated with MNNG for 4 months. The incidence of well-differentiated adenocarcinomas of the stomach was 63-90% in rats treated with MNNG for 4 or more months and 25% in those treated with MNNG for 2 months.
Adenocarcinoma↗
Isolation and structure studies of mutagenic principles in amino acid pyrolysates.
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Amino Acids↗