In vitro sensitivity of various human tumors to 1-beta-d-arabinofuranosy icy tosine and n⁴-behenoy 1-1-beta-d-arabinof uranosylcy tosine

The sensitivities to 1-β-D-arabinofuranosylcytosine (ara-C) and N⁴-behe-noyl-1-β-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 μM 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 μM. The SD activity decreased little at 8.8 μM and decreased individually at 88 μM. The mean of the SD activity at 88 μM 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 < 0.05). BH-AC is converted to ara-C for exertion of the cytotoxic effect and apositive correlation was noted between the SD activities of ara-C and BH-AC (r = 0.825 at88 μM). 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.