Accumulation of polyamine analogs in red blood cells: a potential index of tumor proliferation rate.
It has previously been demonstrated that during Lewis lung carcinoma (3LL) growth, red blood cell (RBC) spermidine (Spd) levels change concominantly with the tumor volume and [14C] Spd accumulates in proportion with the tumor volume, if [14C] putrescine (Put) is administered. In the present study we substituted a non-radioactive analogue for labelled Put with the aim to perform human studies, should the method prove suitable to quantify malignant cell proliferation intensity. 2-Methylputrescine (2MPut) is an excellent substrate of spermidine synthase and is transformed in vivo into methylspermidine (MSpd) and 6-methylspermine (6MSpm). After a single i.p. dose of 2MPut, MSpd accumulated in RBC of mice with 3LL xenografts. The concentration of MSpd correlated directly with tumor progression. No significant amounts of MSpd were found in RBC of normal mice. It appears that 2MPut has the potential to become a new tool in tumor diagnostics.
Moulinoux
J P
JP
Groupe de Recherche en Thérapeutic Anticancèreuse, CNRS SDI, Facultè de Médecine de Rennes I, France.
Quemener
V
V
Havouis
R
R
Guille
F
F
Martin
C
C
Seiler
N
N
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D011700:Putrescine / Q000031:analogs & derivatives / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism
D014408:Biomarkers, Tumor; D013095:Spermidine; D011700:Putrescine