Anti-tumour activity and bone marrow toxicity of chloroethylnitrosocarbamoyl-amino acid derivatives.
The anti-tumour activity of a series of chloroethylnitrosoureas derived from the amino acids alanine and glycine was examined in 3 transplantable adenocarcinomas of the mouse colon. In addition, bone marrow toxicity was assessed using a spleen colony forming unit assay. A spectrum of differing activity-toxicity patterns was demonstrated. At one extreme CNC-glycinemethylamide was shown to exhibit activity against all 3 tumour lines but at the expense of profound bone marrow damage. The other end of the spectrum was represented by CNC-alanylalanine which produced high activity only against the ascitic tumour following intraperitoneal drug administration but in the absence of marrow damage. However, oral administration of this drug led to decreased anti-tumour activity and increased marrow toxicity. These results suggested that differences in the pharmacokinetic behaviour of these compounds were responsible for the differing activity-toxicity patterns. The activity-toxicity pattern exhibited by CNC-alanylalanine indicated that it was a possible candidate for the treatment of local intra-cavitary disease.
Matthew
A M
AM
Clinical Oncology Unit, University of Bradford, West Yorkshire, U.K.
Bibby
M C
MC
Double
J A
JA
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000970:Antineoplastic Agents; C017139:1-(2-chloroethyl)-1-nitrosourea; D005038:Ethylnitrosourea