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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 775 records · Page 43Linked to original sources
PubMed1982

Potent mutagenic activity of nitropyrenes on Chinese hamster lung cells with diphtheria toxin resistance as a selective marker.

Nitropyrenes, which are highly mutagenic in the Salmonella assay, were shown also to be potent mutagens on Chinese hamster lung cells without metabolic activation when resistance to diphtheria toxin was used as a selective marker. Among nitropyrenes tested, 1,8- and 1,6-dinitropyrenes were the most mutagenic, and 1,3-dinitro- and 1,3,6-trinitropyrenes were less active, but showed still much higher mutagenic activity than methyl methanesulfonate or N-methyl-N-nitrosourea. 1-Nitropyrene and 1,3,6,8-tetranitropyrene did not induce diphtheria toxin-resistant mutants at concentrations of up to 20 micrograms/ml.

Animals↗
PubMed1982

Perinatal changes of alpha-fetoprotein concentration in the serum and its synthesis in the liver of analbuminemic rats.

The profile of appearance of disappearance of alpha-fetoprotein (AFP) in the serum of analbuminemic rats, which have a genetically controlled lack of serum albumin, was studied. During the perinatal stage, AFP was present in the serum of analbuminemic rats, its concentration at birth being 10 mg/ml as in normal rats. In analbuminemic rats, the concentration of serum AFP remained at about 10 mg/ml during the first week after birth and then decreased rapidly during the next 2 weeks, becoming undetectable about 4 weeks after birth. In normal rats, the serum AFP concentration reached a maximum of 11.5 mg/ml at birth and then decreased sharply to an undetectable level within 4 weeks after birth, although a small rebound of AFP concentration was observed about 1 week after birth. AFP synthesis in analbuminemic and normal rats was examined by injecting [3H]leucine i.p. and then measuring the radioactivity incorporated into the acid-insoluble fraction and immunoprecipitable fraction using anti-AFP antiserum. In analbuminemic rats, synthesis of AFP amounted to 7.5% of the total protein synthesis at birth and was maintained at about 7% of the total for the first week after birth and then decreased to 2% at 2 weeks after birth. In normal rats, AFP synthesis also amounted to 7.5% of the total protein synthesis at birth but decreased to about 2% at 2 days after birth and then remained at a low level for about 2 weeks. In both normal and analbuminemic rats, AFP synthesis was undetectable at 4 weeks after birth. These data show that AFP synthesis is shutoff after birth irrespective of the serum albumin concentration during neonatal development.

Animals↗
PubMed1982

Intestinal metaplasia of the stomach as a precancerous stage.

Intestinal metaplasia is defined as the appearance of intestinal epithelium in the stomach. Intestinal metaplasia is frequently found in populations with a high incidence of gastric cancer. Macroscopic demonstration of sucrase and trehalase with Tes-tape in many resected stomachs yielded new information for understanding the nature of intestinal metaplasia. Intestinal metaplasia can be classified into two types, complete and incomplete. The former is associated with the presence of sucrase, trehalase, leucine aminopeptidase, alkaline phosphatase, goblet cells and Paneth cells, and the latter with that of sucrase, leucine aminopeptidase and goblet cells, but not trehalase or Paneth cells. Goblet cells in the complete type of intestinal metaplasia contain sialomucin, as does the small intestine, while those in the incomplete type contain sulphomucin and sialomucin, as does the large intestine. Well-differentiated adenocarcinoma is closely related to intestinal metaplasia, especially the incomplete type. Atypical epithelium of intestinal metaplasia has been proposed as a more proximate stage of gastric cancer. Intestinal metaplasia can be diagnosed by staining with dye under endoscopic observation. A reduced level of pepsinogen I in the blood reflects the presence of severe intestinal metaplasia, which is understood to be a sign of high risk of gastric cancer. Intestinal metaplasia is supposed to be produced by components of food. Mutagens/carcinogens such as N-methyl-N'-nitro-soguanidine and N-propyl-N'-nitro-N-nitrosoguanidine can produce intestinal metaplasia in the glandular stomach of rats and gastric cancers. The formation of intestinal metaplasia precedes the appearance of adenocarcinoma in the glandular stomach. Intestinal metaplasia, which is a kind of host reaction to environmental agents, may result either from genetic change - change in DNA structure - or from epigenetic change - change in the differentiation mechanism. Preventive measures could be developed to suppress the development of intestinal metaplasia and to suppress the process of conversion of metaplastic cells to cancer cells.

Cell Differentiation↗
PubMed1982

Mutagenicity of methylglyoxal in coffee.

Major carbonyl compounds from a extract of ground roasted coffee beans were identified as 5-hydroxymethylfurfural, acetol, glyoxal, methylglyoxal and diacetyl. Among these carbonyl compounds, methylglyoxal showed considerable mutagenic activity toward Salmonella typhimurium TA100 without S9 mix (around 100,000 revertants/mg). More than 50% of the total mutagenic activity of coffee can be accounted for by the activity of methylglyoxal.

Aldehydes↗
PubMed1982

Effects of teleocidin and the phorbol ester tumor promoters on cell transformation, differentiation, and phospholipid metabolism.

The potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) and related diterpene phorbol esters have been shown to enhance viral transformation and anchorage-independent growth, inhibit differentiation, and stimulate phosphatidylcholine turnover in various cell culture systems. In the present study, we report that teleocidin, and indole alkaloid isolated from Streptomyces, induces several biological effects similar to those of TPA in cell culture. Both TPA and teleocidin enhanced transformation of a clone of Fischer rat embryo cells (CREF) by a temperature-sensitive mutant of adenovirus type 5 (H5ts125); enhanced the cloning efficiency in agar of E11 cells, a clone of H5ts125-transformed Sprague-Dawley rat embryo cells; inhibited melanogenesis in murine B-16 melanoma cells; inhibited myogenesis in myoblast cultures established from normal human skeletal muscle; and stimulated choline release from prelabeled phospholipids of C3H10T 1/2 mouse cells. In general, TPA and teleocidin were equipotent in inducing these biological effects and were most active in the 3- to 10-ng/ml range, i.e., approximately 10(-8) to 10(-9) M. These studies provide further evidence that teleocidin represents a new class of tumor-promoting agents with properties similar to, if not identical with, those of the phorbol ester tumor promoters. These findings also suggest that cell culture systems can be used to identify new types of tumor-promoting agents in addition to the diterpene phorbol esters.

Adenoviruses, Human↗
PubMed1982

Inhibition of intercellular communication in Chinese hamster V79 cells by teleocidin.

Teleocidin, a mixture of teleocidin A and teleocidin B, was found to block metabolic cooperation between the 6-thioguanine-resistant and the 6-thioguanine-sensitive cells in the Chinese hamster V79 cell system. A teleocidin B preparation containing two isomers exerted the same effect. The dose-response curves of these two compounds were, in general, similar to that of 12-O-tetradecanoyl-phorbol-13-acetate, a powerful mouse skin tumor promoter. Upon hydrolysis with 6M hydrochloric acid containing 4% thioglycolic acid, teleocidin lost most of its ability to block metabolic cooperation. This was probably caused by the conformational change resulting from the rupture of the nine-membered lactam ring of teleocidin.

Alkaloids↗
PubMed1982

The third class of new tumor promoters, polyacetates (debromoaplysiatoxin and aplysiatoxin), can differentiate biological actions relevant to tumor promoters.

Aplysiatoxin is a new class of potent tumor promoter and debromoaplysiatoxin may be a weak promoter. Aplysiatoxin and debromoaplysiatoxin showed the same potency on irritation of mouse ear and induction of ornithine decarboxylase activity on mouse skin, but debromoaplysiatoxin was much weaker than aplysiatoxin in induction of adhesion of HL-60 cells.

Animals↗
PubMed1982

Genetic control of sensitivity of rats to gastrocarcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine.

The administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water induces tumours, mainly adenocarcinomas in the glandular stomach of rats. The sensitivities of different strains of rats to gastrocarcinogenesis induced by MNNG vary: Wistar and ACI strains are sensitive, whereas the Buffalo strain is resistant. Genetic analyses were made on the induction of gastric tumous by MNNG in the ACI and Buffalo strains and their F1 and F2 hybrids. Rats of both sexes, 7-9 weeks old, were given 83 micrograms of MNNG/ml of drinking water for 32 weeks and sacrificed in experimental week 72. The incidences of gastric tumours were as follows: ACI strain, male 80%, female 63%; Buffalo strain, male 29%, female 6%; F1 hybrid, male 35%, female 9%; F2 hybrid, male 65%, female 29%. There were no significant differences in the sensitivities of Buffalo X ACI F1 and ACI X Buffalo F1, or of Buffalo X ACI F2 and ACI X Buffalo F2. These results show that the gene(s) controlling resistance to MNNG is autosomal in the Buffalo strain and is inherited dominantly by F1 and F2 hybrids. In both strains and their hybrids, the incidence of gastric tumours was higher in males than in females.

Adenocarcinoma↗
PubMed1982

Mechanism of appearance of mutagenicity of N-nitrosodiphenylamine with norharman.

The mutagenicity of the carcinogen N-nitrosodiphenylamine (NDPhA) to Salmonella typhimurium TA98 was demonstrated only when norharman, a comutagen, was added to the incubation mixture with S9 mix. N,N-Diphenylamine (DPhA), a denitrosated derivative of NDPhA, was also mutagenic to S. typhimurium TA98 when norharman was present. Twice as many revertants were induced by DPhA with norharman as by NDPhA with norharman. The comutagenic effect of norharman was also observed with N-nitroso-methylphenylamine (NMPhA), N-nitrosoethylphenylamine (NEPhA) and N-nitrosophenylbenzylamine (NPhBeA) and their denitrosated derivatives. NDPhA was converted metabolically to DPhA by S9 mix. Stoichiometric studies indicated that the mutagenicity of NDPhA in the presence of norharman was exerted through DPhA. The denitrosation eyzme activity of NDPhA was mainly recovered in the microsomal fraction, and the enzyme seemed to be a cytochrome P-450 monooxygenase system. Denitrosation reactions of NMPhA, NEPhA and NPhBeA were also demonstrated. The mutagenicities of these compounds with norharman are therefore suggested to be due to a mechanism similar to that of NDPhA with norharman.

Alkaloids↗
PubMed1982

Existence of an optimal dose of dihydroteleocidin B for skin tumor promotion.

The tumor-promoting effects of various doses of dihydroteleocidin B, a catalytically hydrogenated derivative of teleocidin B isolated from Streptomyces mediocidicus, were examined in a two-stage carcinogenicity test on mouse skin. Doses of 1.25, 2.5 and 5.0 micrograms of dihydroteleocidin B dissolved in 0.1 ml acetone were applied twice a week to 7,12-dimethylbenz[a]anthracene-initiated mouse skin for 30 weeks. The maximal cumulative tumor incidence, tumor yield, latent period for 50% cumulative tumor incidence (t50) and amount of promoter needed for 50% cumulative tumor incidence (D50) were used to assess tumor-promoting activity. A dose of 2.5 micrograms of dihydroteleocidin B had the maximal tumor-promoting activity. The optimal dose of dihydroteleocidin B for tumor-promoting activity coincided with the optimal dose for ornithine decarboxylase induction.

Alkaloids↗