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Biomedical subjects

G Yoshii

Publications and source records attributed to G Yoshii.

At least 19 recordsLinked to original sources
PubMed1986

Enhancement of radiation effects by acyclovir.

Acyclovir (ACV), a new antiviral drug, was used to investigate its effect of radiosensitivity in tumors in vivo. In in vivo experiments with Sarcoma-180 transplanted into the ICR mouse and FM3A transplanted into the C3H mouse, ACV enhanced the radiosensitivity of both tumors. In S-180, radiation effects were enhanced by treatment with 100 mg/kg of ACV from 30 min before to 60 min after irradiation. In S-180 treated by 400 mg/kg of ACV, the enhancement ratio was approximately 2.0, as evaluated by the growth delay method. In the FM3A tumor treated by 20 mg/kg of ACV, the enhancement ratio was approximately 1.3, as evaluated by tumor cure (TCD50 assay). ACV is already clinically used as an antiviral drug. Its ability to radiosensitize tumors could therefore have clinical potential when combined with radiotherapy.

Acyclovir↗
PubMed1986

Reaction of the hydrated electron with histone H1 and related compounds studied by e.s.r. and spin-trapping.

The reactions of the hydrated electron with histone H1, protamine and related compounds (poly-L-lysine, poly-L-arginine and poly-D,L-alanine) were investigated by the spin-trapping technique. In order to identify the radical structure of the spin-adducts originating from macromolecules, the usual spin-trapping technique was developed as follows: N2-saturated aqueous solutions of proteins containing sodium formate were X-irradiated (4.5 kGy) in the presence of 2-methyl-2-nitrosopropane (MNP) as a spin-trap. The side-products due to the self trapping of MNP radicals were then removed from the spin-adducts of the proteins by a Sephadex G-25 column. Finally the spin-adducts were enzymatically digested to transform the broad e.s.r. signals due to slow tumbling of nitroxyl radicals to identifiable ones. The e.s.r. spectra obtained for all samples showed that the deaminated radical, R--CH--CO--NH--(R:amino acid side chain), was produced. Furthermore, polyacrylamide gel electrophoresis of the irradiated protamine and histone H1 indicated reduction of molecular size. These results confirm that hydrated electrons react with proteins and induce the deamination reaction which leads to main-chain scission.

Electron Spin Resonance Spectroscopy↗
PubMed1985

Damage in DNA irradiated with 1.2 MHz ultrasound and its effect on template activity of DNA for RNA synthesis.

When aqueous DNA solution was irradiated with 1.2 MHz continuous ultrasound in the presence of cysteamine, the number of ultrasound-induced double-strand breaks of DNA was not influenced, but the number of ultrasound-induced single-strand breaks of DNA was reduced to about one-fifth that of the irradiated control. When the effect of cysteamine on the template activity of the ultrasound-irradiated DNA was investigated, the cysteamine was found to exert a leveling effect on the linear decrease of the template activity against ultrasonic intensity. Since cysteamine was known as an effective radical scavenger, the results of the experiment were regarded to suggest that (1) the double-strand breaks were exclusively induced by the mechanical effect of ultrasound, (2) the majority of single-strand breaks were produced by water radicals arising from cavitation, (3) the initial part in the decrease of the template activity was due to the double-strand breaks arising from mechanical effect, and (4) the further decrease of the template activity depended mainly on the single-strand breaks arising from water radicals.

Cysteamine↗
PubMed1984

Sensitization of Escherichia coli B/r to X-irradiation by 2'-chloro-2'-deoxythymidine.

The sensitizing effect of 2'Cl-TdR has been investigated from the viewpoint of the formation of free radicals at the C-2' position of 2'Cl-TdR when reacted with hydrated electrons. E. coli B/r cells were incubated in growth medium containing 2'Cl-TdR. Centrifugation experiments using CsCl equilibrium density gradients were carried out to confirm the incorporation of 2'Cl-TdR into DNA of the cells. The sedimentation profiles of DNA from cells grown in a medium containing 2'Cl-TdR were found at relatively heavier density positions in comparison with those of DNA from control cells. This result confirms that 2'Cl-TdR was incorporated into DNA. E. coli B/r cells which incorporated 2'Cl-TdR were more sensitive than the control cells for killing by X-irradiation under aerobic conditions. On the other hand, no difference in U.V.-inactivation curves between the cells grown in growth medium containing 2'Cl-TdR and the control cells was observed. From experiments using alkaline sucrose density gradient centrifugation, an increase in the frequency of radiation-induced single strand breaks of E. coli DNA containing 2'Cl-TdR was observed, compared with those of DNA from control cells. These results reveal that the sensitization of 2'Cl-TdR originates from an increase of damage at the sugar moiety in DNA.

Cell Survival↗
PubMed1984

[Problems of antineoplastic effects by PLDR (potential lethal damage repair) inhibitor--pharmacokinetics].

PLDR is one known cause of tumor cell radioresistance. Drugs like ara-A have been reported to inhibit PLDR, thus increasing antineoplastic effects. In this research, ara-A concentration was measured by high-pressure liquid chromatography (HPLC) to investigate its metabolism. Ara-A deaminases in vitro in about 30 minutes, but by using a deaminase inhibitor such as 2'-deoxycoformycin, a fixed level of ara-A can be maintained. Furthermore, the new derivative, ara-AMP, does not deaminase. It is hoped that antineoplastic effects can be effectively increased by maintaining the ara-A concentration through the combined use of deaminase inhibitors and through new derivatives.

Adenocarcinoma↗
PubMed1983

Reactions of the hydrated electron with pyrimidine nucleosides halogenated at the sugar moiety: e.s.r. and spin-trapping with 2-methyl-2-nitrosopropane.

Free radicals produced by the reactions of hydrated electrons with pyrimidine nucleosides halogenated at the sugar moiety (2'-chloro-2'-deoxyuridine and 2'-chlorothymidine) were studied by e.s.r. and spin-trapping. 2-Methyl-2-nitrosopropane was used as the spin-trap. The usual spin-trapping technique was extended to frozen and deoxygenated systems to avoid contamination of the trapped radicals with side-products by spin-trapping 2-methyl-2-nitrosopropane itself. When this method was applied to 2'-chloro-2'-deoxyuridine, a free radical at the C-2' position of the sugar moiety was spin-trapped together with a free radical at the C-5 position of the base moiety. This indicates that hydrated electrons both add to the base moiety and eliminate halogen anions from the halogenated sugar moiety. In the case of 2'-chlorothymidine, however, only a free radical attributed to H-addition at the C-6 position of the thymine base was observed. No radicals produced by the reaction of hydrated electrons with the halogenated sugar could be spin-trapped.

Deoxyuridine↗
PubMed1982

E.S.R. of spin-trapped radicals in aqueous solutions of pyrimidine nucleosides and nucleotides. Reactions of the hydroxyl radical.

Free radicals produced by the reactions of OH radicals with ribose phosphates, pyrimidine nucleosides and nucleotides in aqueous solutions have been investigated by e.s.r. and spin-trapping techniques. OH radicals were generated by U.V. -photolysis of hydrogen peroxide and short-lived free radicals of the samples were spin-trapped by t-nitrosobutane and identified by e.s.r. spectroscopy. For ribose-5'-phosphate and 2' -deoxyribose-5' -phosphate, e.s.r. spectra observed consisted mainly of singles due to -C(5')H2 radicals which were initiated by H-abstraction from the sugar at the C-4' position and formed by the radical transfer to the C-5' position. It has also been shown that OH radicals abstract a hydrogen atom from the sugar at C-1' and C-5' positions. For cytidine, deoxycytidine, 5'-CMP, 3' -CMP and 5' -dCMP, four radicals have been observed and for uridine, deoxyuridine, 5' -UMP, 3' -UMP and 5' -dUMP, the existence of at least three radical species have been established. In contrast to the case of ribose phosphates, no signals due to -C(5')H2 radicals were detected for pyrimidine nucleosides and nucleotides. The results are discussed in relation to a recent mechanism which described OH-induced strand breaks of DNA.

Electron Spin Resonance Spectroscopy↗
PubMed1976

Electron transfer between protein and DNA in gamma-irradiated deoxyribonucleoprotein.

When deoxyribonucleoprotein-proflavine complexes were studied by electron spin-resonance spectroscopy following gamma-irradiation, it was found that stable free radicals were not formed at random on the complex but were preferentially located on proflavine. Since proflavine intercalalated to DNA bases serves as a final acceptor of electrons liberated by ionization, the result of our experiment was regarded as suggesting that the electron transfer from the protein moiety to the DNA moiety occurred in the irradiated deoxyribonucleoprotein.

Animals↗
PubMed1976

Effects of irradiation on RNA synthesis primed by calf thymus deoxyribonucleoprotein treated with salt and salt-urea.

1. The effects of ionizing radiation on the activity of calf thymus templates were examined in a Escherichia coli RNA polymerase system. 2. The template activity of native and 2 M NaCl-5M urea-treated deoxyribonucleoproteins was enhanced by relatively low doses of irradiation, while that of 2 M NaCl-treated deoxyribonucleoprotein was not enhanced by irradiation. 3. The template activity of purified DNA was markedly decreased by irradiation, while that of native deoxyribonucleoprotein, 2 M NaCl-treated, and 2 M NaCl-5 M urea-treated ones were slightly decreased at a higher dose range. The doses for 50% inactivation of these templates were 1.3, 210, 140, and approximately 200 krad, respectively.

Animals↗