In vitro sensitivity of various human tumors to 1-beta-D-arabinofuranosylcytosine and N4-behenoyl-1-beta-D-arabinofuranosylcytosine.
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.
Maehara
Y
Y
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Kusumoto
T
T
Kusumoto
H
H
Anai
H
H
Sugimachi
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D003561:Cytarabine; C015019:enocitabine; D013385:Succinate Dehydrogenase