放射線生物作用とプリン代謝との関係について

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There have been many evidences indicating that the nucleic acid is to be one of the target molecules in radiation injury. The change in radiation sensitivity by modifying purine metabolism was investigated. The purpose of this experiment was to approach the comprehension of the bone marrow injury; the bone marrow was believed to require purine of extra-cellular origin and to be or accordingly to be very sensitive to the purine analogues. Therefore, purine-requiring strain of Saccharomyces cerviciae was adopted in comparison with the bone marrow cells. Purine starvation and administration of purine-analogues at the time of irradiation enhanced the radiosensitivity as follows: 1) The radiation response of the adenine-requiring (not absolute) yeast cells grown in the absence of adenine was greater than that in the presence of adenine. Longer incubation time in the presence of adenine prior to irradiation decreased the radiosensitivity. 2) Nuturally occurring puriens were effective in decreasing the sensitivity in the order of adenine, guanine, hypoxanthine, and adenosine. The purine in the form of base was known to be biologically active after converted into the nucleotide, however this apparently was not seem in this experiment owing perhaps to the low utilization of the adenosine of which it was suggested by the slower growth rate of the cells in the medium containing adenosine instead of adenine. 3) Certain purine-analogues, such as 6-mercaptopurine, 8-azaguanine, and 2-6-diaminopurine enhanced the sensitivity when administered prior to irradiation. 4) 2-C labeled 6-mercaptopurine was incorporated into DNA of the cell, extent of which was highest at 3 hours of incubation. The fact that the radiosensitivity was also highest at this time, however, did not imply the mechanism being enhanced by the incorporation of the analogue into the DNA, because the extent of incorporation and radiosensitivity did not run parallel in the course of incubation time. These results indicated that the starvation of the purine at the time of irradiation sensitized the radiosensitivity, and that certain purine analogues also sensitized it. Referring a lot of papers published coupled with this experiment indicating the role of purine starvation, the contribution of DNA which incorporated purine analogue to a slighter extent than pyrimidine analogue was considered to be very small. And it was suggested that the sensitizing effect of these compounds might result, at least in part, from their induction of a secondary purine starvation caused by the feedback inhibition and by other purine pathway antimetabolic actions of these analogues.
学校法人昭和大学・昭和医学会の論文

放射線生物作用とプリン代謝との関係について

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