Nucleoside analogues. 5. Molecular combination of anti-cancer drugs: activity of 5-fluorouracil/nitrosourea combinations against mouse colon tumours.
Anti-tumour activity of a novel series of molecular combinations, seco-nucleosides where the carrier is a sugar-like fragment linking the pyrimidine anti-metabolite 5-fluorouracil (5-FU) with the alkylating agent N-chloroethyl-N-nitrosourea (CNU), is presented. Three tumour lines, from the mouse adenocarcinoma of the colon (MAC) series, with different sensitivities to 5-FU and CNU were employed. All four molecular combinations tested showed some activity in this system. B 3839, in which 5-FU is linked by a SC--N bond, showed greatest activity against the ascitic tumour MAC 15A but was inactive at non-toxic doses against the solid tumour MAC 13. Activity against MAC 15A was of the same order as that achieved with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. In contrast B 3958, with an OC--N bond, proved inactive against the ascitic tumour but was highly active against MAC 13. The factors responsible for this reversal are as yet unknown.
Double
J A
JA
School of Clinical Oncology, University of Bradford, West Yorkshire, UK.
Bibby
M C
MC
McCormick
J E
JE
McElhinney
R S
RS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005038:Ethylnitrosourea / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051379:Mice; D009705:Nucleosides / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009705:Nucleosides; C017139:1-(2-chloroethyl)-1-nitrosourea; D005038:Ethylnitrosourea; D005472:Fluorouracil