Determination of erythrocyte polyamines as a predictive method in tumour diagnosis. An animal study with chemically induced tumours.
There have been numerous attempts in the past to use polyamine determinations in body fluids for tumour diagnosis. Since spermidine (Spd) and spermine (Spm) are mainly transported in blood by erythrocytes, this study was concerned with the diagnostic possibilities of red blood cell (RBC) polyamine determinations. In tumour-grafted animals we observed that RBC polyamine levels correlated with the tumour mass progression and increased before the tumour was palpable. Discrepancies between the evolution of RBC polyamine levels in tumour-grafted animals and in cancer patients were probably due to the non-continuous growth of the tumours in patients. Therefore, an animal model was sought which mimicked the clinical situation. In the present experiments, ethylnitrosourea induced tumours were used which, in analogy to the clinical situation, had an undetermined time of the appearance in a non-predetermined proportion of the animals. RBC polyamines were determined over a period of 7 months in 154 rats. A total of 2,290 RBC polyamine determinations were performed during this study. The data clearly demonstrate the appearance of elevated Spd concentrations in advance of tumour diagnosis by conventional clinical methods. In 71% of the rats which later developed a tumour, abnormal Spd levels (> 40 nmol/8.109 RBC) preceded, by 35 +/- 31 days, the first clinical symptoms for the presence of a tumour. In 29% of the animals, abnormal RBC Spd concentrations were observed at the time of tumour diagnosis. Elevation of Spm concentrations (> 6 nmol/8.10(9) RBC) was less frequent. RBC polyamine levels did not allow discrimination between malignant and non malignant tumours. This confirms earlier findings that RBC polyamines are markers of the cell proliferation rate, but not for the presence of a malignant tumour. Elevated RBC polyamine concentrations are an index of the intensity of hyperplastic processes, which can be clinically used for the early detection of proliferative phases of tumours, thus allowing timely therapeutic measures.
Quemener
V
V
URA CNRS 1529, Laboratoire de Biologie Cellulaire, Faculté de Médecine de Rennes I, France.
Havouis
R
R
Khan
N A
NA
Martin
C
C
Bouet
F
F
Moulinoux
J P
JP
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002273:Carcinogens / Q000008:administration & dosage; D018450:Disease Progression; D004912:Erythrocytes / Q000737:chemistry*; D005038:Ethylnitrosourea / Q000008:administration & dosage; D005260:Female; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis; D011073:Polyamines / Q000097:blood*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000097:blood; D013096:Spermine / Q000097:blood
D014408:Biomarkers, Tumor; D002273:Carcinogens; D011073:Polyamines; D013096:Spermine; D005038:Ethylnitrosourea; D013095:Spermidine