J.Jpn. Surg. Soc.. 83(4): 331-337, 1982

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Original article

SYNERGISTIC EFFECT OF COMBINED CHEMOTHERAPY AND ENDOCRINE THERAPY ON EXPERIMENTAL TUMORS

The synergistic effect of combined chemo-and endocrine therapy was investigated in vivo and in vitro, using transplantable mammary tumors, and ascitic hepatoma. As for the mammary tumor, MRMT-1 was inoculated subcutaneously into SD rats, and MM102 into C3H mice. As for ascitic hepatoma, AH109A was inoculated subcutaneously into Donryu rats. The concentration of 5-fluorouracil (5-Fu) in the tumor and liver 60 minites after 5-Fu injection increased in animals with ovariectomy in comparison with the sham-operated animals. 5-Fu level in the blood 30 minites after 5-Fu injection in SD rats bearing MRMT-1 was also significantly higher in the group with ovariectomy than in the sham-operated group. Degradation rate of 5-Fu was inhibited by 0.5% liver homogenates obtained from SD rats 48hrs after ovariectomy compared to those from the control group.
These results suggest that the reduction of sex steroids occured following ovariectomy, which in turn affected the metabolism of 5-Fu in the liver with subsequent increase of 5-Fu levels in the liver, blood and tumor.

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