It has been long known that 6-mercaptopurine, a tumor antimetabolite, exerts its inhibitory action towards the growth of tumor tissues of various origins. The mechanism is too complicated because of the multifunctional inhibitory action of the compound to state which of these potential sites of inhibition is the most important in an intact system.
The author intended to determine, in the present work, utilizing human uterus cancer tissue, an aspect of the mechanism of action displayed by 6-mercaptopurine. Cancer tissues were homogenized and incubated with an appropriate amount of 6-mercaptomurine to analyze the size of purine pool of the acid-soluble and nucleic acid nucleotides origins as well as the base co:reposition and ratio of the DNA of the cancer tissue as effected by the presence of G-mer.,aptopurine. Along with these experiment, the effect of the compound on the activity of guanine aminohydrolase in the cancer tissue was. also studied; and the following conclusions were made.
1) 6-mercaptopurine brings a drastic decrease in the content of adenine and guanine of the acid-soluble nucleotide in the uterine cancer tissue, the magnitude of the decline of which is much more pronounced in the adenine than in the guanine content.
2) The purine contents of the nucieic acid do not seem to be affected by the compoun
d. whether it is DNA or RNA.
3) There is no effect observable by the addition of the compound to the uterine cancer
tissue on the base ratio and purine pyrimidine ratio of the DNA molecule in the tissue.
4) 6-mereaptopurine exerts a strong inhibitory action towards the guanine aminohydrolase activity of the uterine cancer tissue.
5) From the above results, it is clear that the tumor antimetabolite interferes the purine metabolism: however, the cancer tissue are well controlled to utilize readily available purines in order to synthesize nucleic acids, even in the presence of the antimetabolite. Therefore, it is suggested that the growth inhibition of tumor tissues brought by 6-MP might be a result of the depletion in the content of available purine nucleotides due to the inhibitory action of the compound, which will lead to the decrease of the cell division rate because of the limiting amount of purine pool.
6) A brief discussion on the nature of the above mechanist. was made.
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