Mikio Shikita

Induction of the Expression of the Interleukin-1β Gene in Mouse Spleen by Ionizing Radiation

Spleen cells freshly isolated from normal mice were irradiated with 20 Gy X rays in culture. Northern blot hybridizations revealed that expression of the interleukin-1 beta (IL-1 beta) gene was induced immediately after irradiation and was increased for 2 h thereafter. Dibutyryl cyclic AMP also caused a persistent expression of the IL-1 beta gene, although it differed from X rays in that it coincidentally induced expression of the c-fos gene, which was not induced by X rays. Activation of either protein kinase C or calmodulin also induced early expression of both IL-1 beta and c-fos. Myeloid cells collected from the spleen of mice with granulocytic leukemia were X-irradiated in culture as above. The leukemia cells responded to X rays as well as to other stimuli in the same manner as the spleen cells, except that IL-1 beta mRNA was no longer detected 30 min after irradiation while c-fos was detectable for 2 h. When the leukemia cells were irradiated twice with a 3-h interval between irradiations, the second irradiation led to prolonged expression of IL-1 beta without inducing c-fos expression. These results suggest that ionizing radiation elicits early expression of the IL-1 beta gene through a mechanism that does not involve protein kinase C or A, or the transcription factor, c-fos. Whole-body irradiation of mice with 50 Gy 137Cs gamma rays also induced IL-1 beta expression in spleen but not in bone marrow or liver, although there was a delay of several hours before it was amply expressed. Furthermore, a delay as long as 24 or 72 h was observed when the radiation dose was reduced to 8.5 or 4 Gy. The results of this in vivo study suggest that the rapidity of expression of the IL-1 beta gene is dependent on the dose of radiation, and that the cells in the body cannot respond to radiation as rapidly as cells in culture.

Specificity of radioprotective and cytotoxic effects of cysteamine in HeLa S3 cells: generation of peroxide as the mechanism of paradoxical toxicity.

Cysteamine at 0.5-5 mM effectively kills

In vitro bioconversion of progesterone-4-C14 to 17α-hydroxyprogesterone and androst-4-ene-3,17-dione in testicular tissue of Tribolodon hakonensis Günther

{\rm HeLa}\ {\rm S}_{3}

Radioprotection of mice by a single subcutaneous injection of heat-killed Lactobacillus casei after irradiation.

cells, while it is much less toxic in higher concentration (30 mM). The toxicity develops gradually with time as peroxide generates in the medium. Addition of catalase and peroxidase to the culture inhibits the toxic effect of cysteamine. The results suggest that the paradoxical cell-killing action of cysteamine can be ascribed to the generation of the peroxide by the compound (

Radiosensitivity of Late Recurrences following Radiotherapy of Murine Fibrosarcomas

2{\rm RSH}+{\rm O}_{2}={\rm RSSR}+{\rm H}_{2}{\rm O}_{2}

Constitutive overexpression of the c-fos gene in radiation-induced granulocytic leukemia in mice

). In higher concentrations, cysteamine protects the cells by decomposing the produced peroxide (

Radioprotective effects of serum thymic factor in mice.

{\rm H}_{2}{\rm O}_{2}+2{\rm RSH}={\rm RSSR}+2{\rm H}_{2}{\rm O}

Toxicity and Radioprophylactic Action of 2-Mercaptoethylguanidine and Its Derivatives in Mice and in HeLa S3 Cells

). Radioprotective effect of cysteamine is not directly related to the cytotoxic action of the compound. The magnitude of dose reduction factor (Y) is a linear function of logarithms of the concentration (X) of the compound (Y = 1.4 log X + 1.2). It is to be noted that the minimum effective concentration is about 0.7 mM and that the protective pow...

Cytochrome P-450 from Bovine Adrenocortical Mitochondria: an Enzyme for the Side Chain Cleavage of Cholesterol I. PURIFICATION AND PROPERTIES

Minced testes of the Japanese dace, Tribolodon hakonensis Gunther, were incubated in vitro with progesterone-4-C14. At least eleven transformation products were isolated by paper chromatography, two of which were identified as 17α-hydroxyprogesterone and androst-4-ene-3,17-dione by their chromatographic behavior and chemical characteristics, as well as on the basis of repeated crystallizations of the substances. The results seem to indicate that there are present the enzymes which catalyze 17α-hydroxylation and side-chain cleavage of progesterone in testicular tissue of the fish. These transformation products suggest that the biochemical pathway from progesterone to androst-4-ene-3,17-dione through 17α-hydroxyprogesterone is the same in fish as it is in mammals.

The Stoichiometry of the Conversion of Cholesterol and Hydroxycholesterols to Pregnenolone (3β-Hydroxypregn-5-en-20-one) Catalysed by Adrenal Cytochrome P-450

Treatment of whole-body gamma-irradiated mice with a preparation of Lactobacillus casei (LC 9018) immediately after irradiation caused a sustained increase in serum colony-stimulating activity which was followed by an enhanced repopulation of granulocyte-macrophage colony-forming cells in the femoral marrow and spleen. Numbers of blood leukocytes, erythrocytes, and platelets were increased earlier in the treated mice than in the controls, and the survival rate was elevated significantly. The radioprotective effect was dependent on the dose of LC 9018 as well as on the dose of radiation. These results demonstrate the value of LC 9018 for the treatment of myelosuppression after radiotherapy or radiation accidents.