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Sho-Saiko-To (SST) is a modified Japanese traditional Chinese herbal medicine containing seven medical plants: Bupleuri radix, Pinelliae tuber, Suxtallariae radix, Zizyphi fructus, Ginseng radix, Glycyrrhizae radix, and Zingiberis recens rhizoma. This preparation has been used in the treatment of some inflammatory diseases of the respiratory system and chronic hepatitis. In the present study, the effects of SST were investigated on the activities of DNA-synthesizing enzymes in 1,2-dimethylhydrazine (DMH)-induced colonic carcinomas in rats. Six-week administration of SST prevented nearly 100% of the body weight loss and the final number of the colonic carcinomas compared to those in the rats treated with DMH alone, and suppressed the enhanced activities of thymidylate synthetase (TS) and thymidine kinase (TK) which were involved in the de novo and salvage pathways of pyrimidine synthesis, respectively, in DMH-induced colonic carcinomas. These results indicate that SST may show directly and/or indirectly inhibitory effects on the development of colonic carcinomas.

Effects of danazol, an isoxazol derivative of the synthetic steroid 17 alpha-ethinyltestosterone, on activities of thymidylate synthetase and thymidine kinase, which are the DNA-synthesizing enzymes included in de novo and salvage pathways of pyrimidine metabolism, respectively, were investigated in rat prostate. Danazol markedly reduced plasma levels of luteinizing hormone and testosterone, and organ weight, both enzyme activities and bromodeoxyuridine-immunoreactive cells which were regarded as the S-phase cells in prostate. These results indicate that danazol shows a property as a potent antigonadotropin.

Thymidine kinase (TK) is a key enzyme in the pyrimidine salvage pathway. High TK activity and the existence of cytosolic isozyme have consistently been observed in rapidly proliferating tissues. Oestrogen treatment induces the moderate increase of activities of mitochondrial TK and the fetal type TK isozyme in immature rat uterus. These results indicate that oestrogen induces the increase of uterine DNA synthesis in both cytosol and mitochondria in immature rats.

A lignin-related cone extract of pine (Pinus parviflora Sieb et Zucc) (FrVI) or a synthetic lignin (DHP-FA) (175 micrograms/0.1 ml 0.9% NaCl solution) was injected intravenously to SHN mice bearing spontaneous mammary tumours three cycles each with consecutive 3 days of treatment and 4 days of interruption. Activities of both thymidylate synthetase (TS) and thymidine kinase (TK), i.e., DNA synthesizing enzymes in de novo and salvage pathways of pyrimidine metabolism, respectively, were apparently decreased in mammary tumours of FrVI-treated mice compared to those of the control mice bearing tumours without treatment. While the percent change of mammary tumour size during the experiment differed little among groups, both FrVI and DHP-FA prevented tumours from ulceration. Furthermore, the development and growth of preneoplastic mammary hyperplastic alveolar nodules were decreased by the treatments of both agents. They showed no toxicity. All results suggest that these lignin-related compounds, especially FrVI, may be useful as chemopreventive agents, with some improvement of administration method, and/or for employment in combination with any other agents.

Ectopic pituitary isografts (EPI) have been found to induce a high incidence of uterine adenomyosis in SHN mice. All the SHN mice given EPI in the right uterus at 40 days of age developed uterine adenomyosis, and more than 80% of mice showed the genesis of subserosal nodules, an advanced state of adenomyosis, 65 days after EPI. Activities of both thymidylate synthetase and thymidine kinase, i.e. DNA-synthesizing enzymes in de novo and salvage pathways of pyrimidine metabolism, respectively, were significantly increased in EPI-induced uterine adenomyosis to approximately 2-fold those in normal control uteri. Bromodeoxyuridine-immunoreactive cells were regarded as the cells in S phase, and the number in the endometrial epithelium and stroma in EPI-induced uterine adenomyosis was more than 1.5-fold that in normal control uteri. EPI may affect the genesis of uterine adenomyosis generally, but not locally, because there were no differences between the right uterus with EPI and the left without EPI in the incidence of adenomyosis, histology or DNA-synthesizing enzyme activities.