Effects of postoperative adjuvant chemotherapy on liver regeneration in partially hepatectomized rats

Five-fluorouracil (5-FU) was given to rats at various periods following two-thirds hepatectomy and the effects of this drug on the regenerating liver were investigated. In one group of rats, two-thirds hepatectomy was carried out (Group I). In four other groups, 20 mg/kg 5-FU was given intravenously three times: 0, 24, 48 hours (Group II); 12, 36, 60 hours (Group III); 24, 48, 72 hours (Group IV); and 3, 4, 5 days (Group V) after the same operation. The peaks of DNA synthesis and mitoses of liver cells were noted on the first postoperative day in Groups I, IV and V. Persistent suppression and delay of DNA synthesis was induced in Groups II and III, while in Group IV, DNA synthesis and liver cell divisions were suppressed temporarily after the drug administration but recovered thereafter. There was no significant suppression in Group V. The serum albumin levels and survival rates paralleled the DNA synthesis. These results indicate that in case of postoperative adjuvant chemotherapy, great care must be directed to the time when DNA synthesis and mitosis of hepatocytes have not yet reached their peaks, because adjuvant chemotherapy in this period may be life-threatening.