Published in Cancer Detection and Prevention 2000; 24(6):542-548.

Blood Polyamine Levels After Oral Ornithine Load, Diagnostic Marker of Hyperproliferative Premalignant and Malignant Stages in a Model of Colon Carcinogenesis

René Schleiffer, PhD, Benoit Duranton, PhD, Francine Gossé, MS, Michel Hasselmann, MD, and Francis Raul, PhD

ULP/CJF INSERM 95-09, Laboratoire du Contrôle Métabolique et Nutritionnel en Oncologie Digestive, Strasbourg-Cedex, France

Address all correspondence to: René Schleiffer, PhD, CJF INSERM 95-09, IRCAD, Hôpitaux Universitaires 1, Place de l’Hôpital, BP 426, F67091 I Strasbourg-Cedex, France.

ABSTRACT: This study was performed to determine whether a single oral dose of omithine (Orn), the substrate of omithine 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 Om, blood PUT, but not SPD and SPM, concentrations were significantly higher in DMHtreated 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.

KEY WORDS: putrescine, omithine, colorectal cancer, l, 2-dimethylhydrazine.