Effects on DNA and RNA after the administration of two different schedules of 5-fluorouracil in colorectal cancer patients.
OBJECTIVE
5-Fluorouracil (5-FU) has two major mechanisms by which it exerts its anticancer activity. One mechanism operates through the inhibition of thymidylate synthetase (TS) by the active metabolite 5-fluorodeoxyuridine 5'-monophosphate. The other mechanism is the incorporation of 5-FU into RNA. Using tumor tissue specimens from colon carcinoma patients given 5-FU by two different modes of administration, we investigated the effects of 5-FU on DNA and RNA.


METHODS
Group A patients received 200 mg/day of 5-FU as a rapid infusion for 5 days preoperatively, and group B patients received 200 mg/day of 5-FU as a continuous infusion for 5 days preoperatively. Postoperatively, we analyzed the 5-FU concentration, 5-FU incorporation into RNA (F-RNA), and TS inhibition rate (TSIR) in normal tissue, cancerous tissue, and lymph nodes.


RESULTS
The F-RNA concentration in tumor tissue from group A patients was higher than in tissue from group B patients. The TS concentrations in tumor tissue were significantly higher than in non-tumor tissue in both groups. In lymph nodes, the TSIR of group A was 78.5% and that of group B was 55.2%, a significant difference.


CONCLUSIONS
Bolus injection can be considered to be more effective with respect to RNA damage in tumor tissue. Especially in cases involving lymph node metastasis, bolus injection was effective with respect to DNA damage as well as RNA damage.
Hoshino
Seiichirou
S
Second Department of Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Japan. shoshino@fukuoka-u.ac.jp
Yamashita
Yuuichi
Y
Maekawa
Takafumi
T
Shirakusa
Takayuki
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012334:RNA, Neoplasm / Q000187:drug effects*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D013940:Thymidylate Synthase; D005472:Fluorouracil