Allopurinol-induced pyrimidinuria in cancer patients.
Allopurinol induced pyrimidinuria is a sensitive and specific test that identifies the increased de novo pyrimidine mononucleotide biosynthesis accompanying ornithine trans carbamylase deficiency. We hypothesize that the increased de novo DNA synthesis characteristic of malignant tumors can be detected using this method. Eleven cancer patients and a 30 subject control group were studied. The allopurinol test protocol consists of five urine collection periods--a baseline collection after which time a 300 mg dose of allopurinol is taken, followed by collection of four 6 hour fractional urine collections. Orotate, orotidine and creatinine were measured on the samples. Eight of 11 patients had significantly elevated urine levels of either orotate or orotidine either prior to challenge with allopurinol or during one of the time periods. The allopurinol test for this unstratified group has a sensitivity of 0.73 and a specificity of 1.0. This observational and preliminary report suggest that further study of the potential significance and usefulness of the allopurinol test in patients at risk for or with malignancy is warranted.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore 21205, USA.
M A
MA
Carducci
M
M
Choti
N E
NE
Maestri
S W
SW
Brusilow
D000138:Acidosis / Q000139:chemically induced / Q000652:urine; D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000652:urine*; D009963:Orotic Acid / Q000652:urine; D011743:Pyrimidines / Q000652:urine*; D014529:Uridine / Q000031:analogs & derivatives / Q000652:urine
D000963:Antimetabolites; D011743:Pyrimidines; D009963:Orotic Acid; D000493:Allopurinol; D003404:Creatinine; C008714:orotidine; D014529:Uridine