Decarboxylated-S-adenosylmethionine excretion: a biochemical marker of ornithine decarboxylase inhibition by alpha-difluoromethylornithine.
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.
D000368:Aged; D003404:Creatinine / Q000652:urine; D000518:Eflornithine / Q000494:pharmacology / Q000627:therapeutic use* / Q000652:urine; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000652:urine; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000652:urine; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives* / Q000652:urine
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C012702:S-adenosyl-3-methylthiopropylamine; D012436:S-Adenosylmethionine; D003404:Creatinine; D000518:Eflornithine