Blood polyamine levels after oral ornithine load, a diagnostic marker of hyperproliferative premalignant and malignant stages in a model of colon carcinogenesis.
This study was performed to determine whether a single oral dose of ornithine (Orn), the substrate of ornithine decarboxylase (ODC), increases blood concentrations of polyamines premalignant stage, and whether blood polyamine levels could be used as predictive markers of cancer development. Male Wistar rats were divided into two groups, control and 1,2-dimethylhydrazine (DMH)-treated rats. DMH (20 mg/kg body weight) was injected intraperitoneally once weekly for 10 weeks. Five, 7, and 10 weeks after the last injection when premalignant aberrant crypt foci have developed in the colon, blood levels of putrescine (PUT), spermidine (SPD), and spermine (SPM) were estimated before and after an oral load of ORN. The results showed that after a single oral load of Orn, blood PUT, but not SPD and SPM, concentrations were significantly higher in DMH-treated rats compared with control rats, indicating enhancement of ODC activity. These results support the view that the increased blood concentration of PUT after administration of Orn may be a useful marker to detect hyperproliferative premalignant and malignant stages of cancer development.
Schleiffer
R
R
ULP/CJF INSERM 95-09, Laboratoire du Contr le Métabolique et Nutritionnel en Oncologie Digestive, Strasbourg, France.
Duranton
B
B
Gossé
F
F
Hasselmann
M
M
Raul
F
F
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D000236:Adenoma / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D001711:Biotransformation; D001835:Body Weight; D002455:Cell Division; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D003111:Colonic Polyps / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D018450:Disease Progression; D005215:Fasting / Q000097:blood; D006965:Hyperplasia; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009952:Ornithine / Q000493:pharmacokinetics; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000097:blood*; D011230:Precancerous Conditions / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D011700:Putrescine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013095:Spermidine / Q000097:blood; D013096:Spermine / Q000097:blood
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011073:Polyamines; D013096:Spermine; D009952:Ornithine; D009955:Ornithine Decarboxylase; D019813:1,2-Dimethylhydrazine; D013095:Spermidine; D011700:Putrescine