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Biomedical subjects

M Nakadate

Publications and source records attributed to M Nakadate.

At least 37 records · Page 2Linked to original sources
PubMed1983

Effect of phenobarbital and 3-methylcholanthrene on the hepatic microsomal metabolism of N-nitrosodimethylamine, N-nitrosomethylbutylamine and N-nitrosomethylbenzylamine.

The effect of phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment on dealkylations of N-nitrosodimethylamine (NDMA), N-nitrosomethylbutylamine (NMBuA) and N-nitrosomethylbenzylamine (NMBeA) was investigated in rat hepatic microsomes. PB increased the demethylation and the debutylation of NMBuA and the debenzylation of NMBeA. MC increased the debutylation of NMBuA and the debenzylation of NMBeA. However, MC decreased the demethylation of NMBeA. The demethylation of NDMA was not changed by the pretreatment of the inducers. These results suggest that the dealkylations of these nitrosamines are catalyzed by several enzymes, which probably depend on different cytochrome P-450 species.

Animals↗
PubMed1983

Induction of angiogenic tumors in the duodenum of female Donryu rats by continuous oral administration of N-isobutyl-N-nitrosourea.

Four groups of female Donryu rats were continuously given 400, 200, 100 or 0 ppm N-isobutyl-N-nitrosourea (iso-BNU) in their drinking water, and were examined for the development of tumors. The incidence of digestive tract tumors was 25/28 (89%), 14/24 (58%), 6/25 (24%) and 0/17 (0%), in the 400, 200, 100 and 0 ppm groups, respectively. The predominant type of digestive tract tumor was angiogenic, and a few were of the epithelial type. A dose-effect relationship was clearly demonstrated not only in the incidence of digestive tract tumors but also in the average survival period of rats with these tumors.

Administration, Oral↗
PubMed1982

Vascular tumors of the spleen and other neoplasms induced in Syrian golden hamsters by 1-propyl-1-nitrosourea.

Continuous administration of either 400 ppm or 100 ppm 1-propyl-1-nitrosourea (PNU) in drinking water to Syrian golden hamsters, from 11 weeks of age, induced tumors of the spleen, forestomach, duodenum, and vagina. The tumor incidences in the spleen were 33 of the 36 males (91.7%) and 34 of the 37 females (91.9%) in the 400 ppm group and 32 of the 40 males (80%) and 26 of the 34 females (76.5%) in the 100 ppm group. In addition, tumors were induced in the forestomach and duodenum of both sexes and in the vagina in females. Histologically, the tumors were classified as hemangioendotheliomas of the spleen, squamous cell papillomas and carcinomas of the forestomach, adenocarcinomas of the duodenum, and squamous cell papillomas and carcinomas of the vagina. Compared to results previously reported in rats, the present results reveal a remarkable species difference in the organ specificity of PNU.

Adenocarcinoma↗
PubMed1980

Differential mutagenicities of 6 N-nitroso-N-alkylurea derivatives in Escherichia coli strains with different DNA-repair capacities.

Reverse mutations to prototrophy by, and killing effects of, 6 N-nitroso-N-alkylurea derivatives such as NMU, NEU, NPU, NBU, NIBU and NAU were studied with E. coli strains H/r30R (wild-type), Hs30R (uvrA-), O16 (polA-) and NG30 (recA-). Both strains polA- and recA- were far more sensitive to killing by the 6-compounds than were the wild-type and uvrA- strains, and there was no difference in the sensitivity between the latter 2 strains. NMU was mutagenic in all 4 strains; wild-type, uvrA- and polA- strains were almost equally mutable but the compound was slightly mutagenic in the recA- strain. The other 5 compounds, NEU, NPU, NBU, NIBU and NAU, caused hardly any mutation in the recA- strain. NEU, NPU and NBU were equally mutagenic in the wild-type, uvrA- and polA- strains; however, NIBU and NAU were more mutagenic in the uvrA- than in the wild type or polA-. From the differential mutagenicities and lethalities induced by the 6 N-nitroso-N-alkylureas into the 4 tester strains, mutational patterns of the compounds can be classified into 3 types.

DNA Repair↗
PubMed1980

Induction of duodenal tumors in F344 rats by continuous oral administration of N-ethyl-N-nitrosourea.

Forty male and 40 female inbred F344 rats were given a solution of 400 mg N-ethyl-N-nitrosourea/liter in their drinking water. Digestive tract tumors were induced in 32 males (an incidence rate of 80%) and in 28 females (an incidence rate of 70%). Among these digestive tract neoplasms, duodenal tumors occurred most frequently. Most were of the epithelial type, such as adenoma or adenocarcinoma. Tumors in hematopoletic organs were also found in 15 males (38% incidence) and in 17 females (43% incidence).

Animals↗
PubMed1980

Induction of digestive tract tumors and leukemias in Donryu rats by administration of 1-amyl-1-nitrosourea in drinking water.

The effects of administration of 1-amyl-1-nitrosourea (ANU) at doses of 400, 200, 100 and 0 ppm in the drinking water to Donryu rats of both sexes were studied. Tumors developed in 166/205 (81%) rats that received ANU, as compared with 9/34 (27%) control rats. The incidence of digestive tract tumors was highest (76%), followed by hematopoietic tissue (11%) and liver (9%) tumors. In females, mammary tumors were also found. There appeared to be a dose-response relationship among the 3 treated groups as regards the incidence of tumors of the hematopoietic tissues and the average survival time.

Animals↗
PubMed1980

Induction of duodenal-tumors and thymomas in Fischer rats by continuous oral administration of 1-propyl-1-nitrosourea.

Male and female F344/DuCrj rats were given 400 ppm solution of 1-propyl-1-nitrosourea continuously in their drinking water. The incidence of digestive tract tumors was as high as 32/36 (89%) and 33/39 (85%) in male and female rats, respectively. Among these, duodenal tumors were induced most frequently, and most of them were adenocarcinoma followed by adenomas and hemangiogenic tumors. Thymomas were found in 27 (75%) males and 14 (36%) females. The lymphocytic type thymoma was the most frequent, and epithelial or mixed types were found only in 8 females. Other tumors induced were mainly in the ear ducts and lung, and the incidence was less than 13%.

Adenocarcinoma↗
PubMed1979

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↗
PubMed1978

Sensitivity difference of rat ascites hepatoma AH-13 and mouse leukemia L-1210 to nitrosourea derivatives.

The structure-activity relationship in different sensitivity of AH-13 and L-1210 to nitrosourea nad related derivatives was examined. N-Methyl-N-nitrosoureido derivatives, such as 1-methyl-1-nitrosourea (MNU) and 1, 1'-polymethylene-bis(3-substituted 3-nitrosourea), were inactive against AH-13 and slightly active against L-1210. On the contrary, 1, 1'-polymethylene-bis(3-substituted 1-nitrourea) derivatives were more active against AH-13 than against L-1210. The nitrosoureas which had bis(2-chloroethyl) group at the terminal were highly active against AH-13 and L-1210. One of denitrosated derivatives, 1, 1'-ethylene-bis[3-(2-chloroethyl)urea], was active against AH-13 alone. In addition, diisocyanates, nitrourea, ammonium carbamate, and 1-methyl-1-nitrourea, which are related to the nitrosourea compounds, were also tested for their activity against AH-13 and L-1210. Diisocyanates and nitrourea were active against AH-13 alone, while other compounds were all inactive.

Animals↗