A
monoclonal antibody specific for a modified
nucleoside,
1-methyladenosine, was prepared and characterized. This antibody, termed AMA-2, reacts with
1-methyladenosine and
1-methyladenine but not with other
nucleosides, particularly methylated adenosines other than
1-methyladenosine and methylated guanosines, tested in this investigation. In our experiments, AMA-2 was used in an
enzyme-linked
immunosorbent assay (ELISA) system for the quantitation of the levels of
1-methyladenosine in urine. Sensitivity was in the picomole range and accuracy was nearly equal to that of the high-performance liquid chromatography (HPLC) assay system. Urinary levels of
1-methyladenosine in healthy donors and patients with various advanced
cancers were determined by the inhibition ELISA. The amount of
1-methyladenosine in urine of 33 healthy donors was 1.91 +/- 0.66 nmol/mumol
creatinine. In 54% (51/94) of patients, urinary
1-methyladenosine was elevated above the mean plus 2 standard deviations for the healthy donors (3.23 nmol/mumol
creatinine). In patients with
leukemia,
esophageal cancer,
stomach cancer,
colon cancer, and
bladder cancer, urinary levels of
1-methyladenosine were significantly elevated. In patients with
leukemia, urinary
1-methyladenosine levels changed almost in parallel with the change in the clinical response during
chemotherapy. These results suggest that urinary
1-methyladenosine might be useful in monitoring the effectiveness of
therapy.