Prevention of 5-FU induced toxicity in C3 H/HE mice with interferon or with interferon inducers (poly 1: C, OK-432, Lentinan)
Akimoto, M.; Ueki, H.; Nakajima, Y.; Matano, S.; Ewasaki, H.; Abe, R.; Kasai, M.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 11(7): 1462-1467
1984
ISSN/ISBN: 0385-0684 PMID: 6204597 Document Number: 221574
It is well known that all cell lines, normal as well as malignant, have a sensitivity to the growth-inhibitory effect of Interferon, or Interferon inducers. 5-FU is a widely used anticancer drug considered to be a cell cycle-specific agent. We speculated that the antiproliferative effect of Interferon or Interferon inducers might affect the activity of 5-FU and diminish the uncomfortable side-effects of this agent. Initially this experiment, we observed the mortality rate in mice after administration of 5-FU alone, or 5-FU plus Interferon (alpha inducers). We then carried out cytofluorometric observation of bone marrow cells, and finally studied the influence of Interferon (or inducers) on the anticancer effects of 5-FU against MM48 tumors in C3/He mice. Findings were as follow: 1) Administration of beta-type Interferon for 2 days, following the administration of a toxic dose (140 mg/kg/w) of 5-FU, revealed significant protection from mortality in C3H/He mice. This effect was also observed when Interferon inducers (Poly I: C, OK-432, Lentinan) were administered with 5-FU. Body weight loss was 10.4% at nadir in mice treated with 5-FU alone, while there was a body weight gain of 36.3% in mice treated with 5-FU plus Interferon. 2) Cytofluorometry of bone marrow cells obtained from mice femur at timed intervals after the administration of OK-432, or Lentinan indicated that these drugs inhibited the entry of cells into the S-phase, causing then to accumulated in the G0.G1-phase during the first 48 hours. 3) Histological findings of intestinal mucosa in mice showed prominent destruction after bolus injection of 350 mg/kg of 5-FU alone, while these findings were not observed in mice after the bolus injection of 350 mg/kg of 5-FU combined with Interferon. 4) The tumor volume ratio (T/C) was significantly reduced in the group treated with 5-FU alone as well as that treated with 5-FU combined with Interferon (or inducers) in C3H/He mice bearing MM48 tumors. All mice were dead about 2 weeks after administration of 5-FU alone, while all mice treated with 5-FU plus Interferon (or inducers) were alive in the same period. From these results, we speculate that Interferon, or Interferon inducers play an important role in the prevention of side effects of cell cycle-specific cytotoxic drugs like 5-FU, without decreasing their anticancer activity.