Decarboxylated-S-adenosylmethionine excretion: a biochemical marker of ornithine decarboxylase inhibition by alpha-difluoromethylornithine.

Abstract

In an attempt to define a biochemical marker of ornithine decarboxylase inhibition in humans, alpha-difluoromethylornithine hydrochloride (DFMO), an irreversible ornithine decarboxylase inhibitor, was infused i.v. in seven cancer patients over 10-day courses at doses of 10-90 g/day and 24-h urinary excretion of polyamines and decarboxylated-S-adenosylmethionine was determined before, during, and after treatment. DFMO produces marked increases in urinary decarboxylated-S-adenosylmethionine excretion, up to 84 times pretreatment values. This response appears to be time dependent, requiring several days to reach a maximum and lasting at least 4-5 days after stopping DFMO. In contrast, urinary excretion of the polyamines putrescine, cadaverine, spermidine, N1-monoacetylspermidine, N8-monoacetylspermidine, and spermine, were not consistently altered by DFMO. We conclude that urinary excretion of decarboxylated-S-adenosylmethionine represents a valid biochemical indicator of ornithine decarboxylase inhibition in humans, whereas urinary polyamines are of no value.

• Authors: K D Haegele, T A Splinter, J C Romijn, P J Schechter, A Sjoerdsma
• Journal: Cancer research (Cancer Res) Vol. 47 Issue 3 Pg. 890-5 (Feb 01 1987) ISSN: 0008-5472 [Print] United States
• PMID: 3100028 (Publication Type: Journal Article)

Chemical References

• Ornithine Decarboxylase Inhibitors
• Polyamines
• S-adenosyl-3-methylthiopropylamine
• S-Adenosylmethionine
• Creatinine
• Eflornithine

Topics

• Aged
• Creatinine (urine)
• Eflornithine (pharmacology, therapeutic use, urine)
• Female
• Humans
• Kinetics
• Male
• Middle Aged
• Neoplasms (drug therapy, enzymology, urine)
• Ornithine Decarboxylase Inhibitors
• Polyamines (urine)
• S-Adenosylmethionine (analogs & derivatives, urine)