The sensitivities to 1-beta-D-arabinofuranosylcytosine (
ara-C) and N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a masked compound of
ara-C, were determined in 33 human
tumor tissues (11 gastric, 6
colorectal cancers and 16
malignant lymphomas), using the in vitro
succinate dehydrogenase inhibition test. The
succinate dehydrogenase (SD) activity of the
tumor tissues was assayed following exposure to the
drug at 8.8 or 88 microM for 3 days and the sensitivity was considered positive when the SD activity decreased to below 50% of that of the control cells at 88 microM. The SD activity decreased little at 8.8 microM and decreased individually at 88 microM. The mean of the SD activity at 88 microM was 65.7 +/- 11.5% for
ara-C and 61.4 +/- 14.5% for BH-AC in
gastrointestinal cancers, and 63.8 +/- 16.0% for
ara-C and 58.3 +/- 18.3% for BH-AC in
malignant lymphomas with a statistically significant difference (p less than 0.05). BH-AC is converted to
ara-C for exertion of the cytotoxic effect and a positive correlation was noted between the SD activities of
ara-C and BH-AC (r = 0.825 at 88 microM). The chemosensitivity varied with the tissue and 18% of the tissues were sensitive to
ara-C, 27% to BH-AC and 15% were sensitive to BH-AC but resistant to
ara-C. Our findings show that
ara-C and BH-AC are equally
cytostatic to human
tumors. The sensitivity test of
ara-C and BH-AC enables one to determine which
drug is best suited for individual patients.