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M Akao

Publications and source records attributed to M Akao.

At least 91 records · Page 5Linked to original sources

A search for nuclear RNA lost in azo dye-induced transplantable hepatoma.

Studies were conducted to characterize the nuclear RNA (nRNA) species that were present in rat liver but absent in the hepatoma. Nuclear RNA was compared between Donryu rat liver and AH136B hepatoma, an azo dye-induced transplantable cell line, by DNA-RNA competitive hybridization. The hepatoma lacked 13-14% of nRNA according to measurements of radioactivity of the hybridized 32P-labeled liver nRNA, and this loss was shown to be due to the failure to transcribe such RNA rather than to the deletion of the relevant DNA in the genome. Characterization of the lost RNA was first attempted by fractionating liver nRNA by density gradient sedimentation and polyacrylamide gel electrophoresis. A comparison of the additive effects of the fractionated RNA's in the competitive hybridization indicated that the pertinent RNA was present in the large RNA molecules (greater than 14S), not in the low molecular weight RNA's. Then poly(A) nRNA was found to show a strong additive effect in the competitive hybridization while nucleolar RNA showed little additive effect, indicating that the pertinent RNA was present in the heterogeneous nRNA, not in the ribosomal precursor. Further characterization was done by fractionating DNA with regard to the repetition in the genome. A comparison of the competitive hybridizations on the fractionated DNA's showed that the loss occurred mostly in RNA transcribed from highly repetitive DNA. In conclusion, the RNA species lost in the hepatoma were components of heterogeneous nRNA transcribed from highly repetitive DNA.

Animals↗

Inhibitory effect of fumaric acid on 3-methyl-4'-(dimethylamino)-azobenzene-induced hepatocarcinogenesis in rats.

Fumaric acid (FA) was examined for its effect on hepatocarcinogenesis in rats fed 3-methyl-4'-(dimethylamino)azobenzene (3-Me-DAB). Male DONRYU rats were given approximately 0.5 g 3-Me-DAB by being fed a diet containing 0.06% 3-Me-DAB for 50 days; they were then given a diet containing 1% FA and drinking water containing 0.025% FA for 51 weeks. The administration of FA effectively suppressed the development of hepatocellular carcinoma, hyperplastic nodules, and hyperplastic areas in the livers of rats fed 3-Me-DAB.

Animals↗

Toxicity of mitomycin C and anti-intoxication by fumaric acid in liver and kidney cellular fine structure.

The previous study indicated that the toxic symptoms in ICR mice given two ip injections of 4 mg/kg of mitomycin C at an interval of 48 hr were reduced by the concurrent administration of 40 mg/kg of fumaric acid. In the present study, are described the changes of subcellular components and organella in the liver and kidney at 4 days after the 2nd injection. The liver treated with mitomycin C showed perinuclear irregularity, aggregation of chromatins, and abnormal cytoplasmic organella (e.g., swelling of mitochondria and dilatation of rough endoplasmic reticulum). Focal localization of rough endoplasmic reticulum was noted. The concurrent administration of fumaric acid reduced the incidence of such deleterious changes. Increases in the number of nucleoli and normal cytoplasmic organella were evident. The kidney treated with mitomycin C showed decrease of chromatins and edematous nuclear matrix. The cytoplasmic organella were swollen. The action of fumaric acid against mitomycin C intoxication was more apparent in the kidney. Chromatins and nucleoli developed well and other subcellular organella appeared completely normal.

Animals↗

Inhibitory effect of fumaric acid on forestomach and lung carcinogenesis by a 5-nitrofuran naphthyridine derivative in mice.

The inhibitory effect of fumaric acid (FA) on carcinogenesis by potassium 1-methyl-7-[2-(5-nitro-2-furyl)vinyl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (trans, NFN) was examined histologically with male ICR/JCL mice. NFN was fed to mice at a dose level of 0.012% in the diet for 14 weeks. These mice were then divided into 2 groups. One group was given a basal diet, and the other group was given a diet containing 1% FA in the subsequent 39 weeks. In the group of 30 mice fed NFN alone, squamous cell carcinomas were found in the stomachs of 7 mice, multiple papillomas in the stomachs of 13 mice, and multiple and large papillary adenocarcinomas in the lungs of 27 animals. The administration of FA suppressed the NFN-induced stomach and lung carcinogenesis. In the group of 32 mice fed NFN and FA, no stomach tumors developed except 1 early-stage of squamous cell carcinoma. In the lungs, only a small focus of mild atypical hyperplasia and a few early-stage adenocarcinomas were noted in 7 and 11 animals, respectively.

Adenocarcinoma↗

Analysis of loss of nuclear RNA in azo dye-induced hepatoma by DNA-RNA competitive hybridization.

DNA-RNA hybridization studies, using nuclear RNA's (nRNA's) labeled in vivo and in vitro with high specific radioactivities, were performed to compare the nRNA populations of normal rat liver, livers treated with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), and 3'-Me-DAB-induced hepatomas. The study with normal liver nRNA labeled by i.p. injection of [3H]orotic acid indicated that the nuclei of a 3'-Me-DAB-induced transplanted hepatoma, AH136B, lacked some RNA species present in normal liver nuclei. No qualitative difference in thee RNA populations was seen between normal liver and the livers of rats fed a carcinogenic amount of 3'-Me-DAB, either alone or in combination with 4-nitrostilbene which enhanced the azo dye carcinogenesis. Then, nRNA's of both normal liver and AH136B hepatoma were labeled in vitro by phosphorylation with polynucleotide kinase and adenosine 5'-[gamma-32P]triphosphate. The competitive hybridization with 32P-labeled normal liver nRNA was competed, and the deletion of RNA in the nuclei of AH136B hepatoma or 3'-Me-DAB-induced primary hepatoma was estimated to be 15% or more in the measure of radioactivity of the hybridized normal liver nRNA. 32P-labeled AH136B hepatoma nRNA was completed completely by liver nRNA's, suggesting that no unique RNA species were present in the hepatoma nuclei.

Animals↗

Antitumor and anti-intoxication activities of fumaric acid in cultured cells.

Fumaric acid, isolated as the active component of Capsella bursa-pastoris herb for inhibiting the solid growth of Ehrlich tumor in mice, was found to reduce markedly the growth and viability of Ehrlich, MH134, and L1210 mouse tumor cells in culture at concentration of 0.3 approximately 1.2 mg/ml. In contrast, fumaric acid at these concentrations in the culture medium had no deleterious effect on the monolayer development of mouse and chick embryo cells but exhibited activity to enhance the recovery of the cells from the toxic effects of mitomycin C, aflatoxin B1, N-methyl-N'-nitro-N-nitrosoguanidine, and potassium 1-methyl-7-[2-(5-nitro-2-furyl) vinyl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.

Animals↗

Enhancing and inhibitory effects of some stilbene and steroid compounds on induction of hepatoma in rats fed 3'-methyl-4-(dimethylamino)azobenzene.

Examinations were made on substances that enhance or inhibit the induction of hepatoma in rats previously fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) for a brief period. The substances tested were stilbene, 4-nitrostilbene, 4,4'-dihydroxystilbene, diethylstilbestrol, 17beta-estradiol, and methyltestosterone. Male Donryu rats were fed 0.5 g of 3'-Me-DAB by being maintained on a diet containing 0.06% 3'-Me-DAB, and then they were fed 0.25 or 0.5 g of a test substance with the basal diet. Comparison of the development and yield of hepatomas indicated that 4-nitrostilbene and methyltestosterone had an activity of enhancing 3'-Me-DAB carcinogenesis, whereas diethylstilbestrol and 17beta-estradiol had an activity to retard it. Other substances showed no such activities. The enhancement by 4-nitrostilbene and inhibition by diethylstilbestrol of 3'-Me-DAB carcinogenesis was correlated with their effect on liver nucleic acid metabolism. Feeding of 4-nitrostilbene caused a selective inhibition of Mn2+-(NH4)2SO4-activated RNA polymerase activity of liver nuclei and reduced liver RNA content. The deleterious alteration of liver RNA metabolism was followed by the enhancement in the incorporation of ip-injected 3H-thymidine into DNA of liver nuclei. On the other hand, feeding of diethylstilbestrol increased tissue RNA content without effect on RNA polymerase activity of liver nuclei, and had an activity of increasing the incorporation of 3H-thymidine into DNA. The possible implication of these results with regard to the enhancement and inhibition of hepatocarcinogenesis is discussed.

Animals↗