Maehara Y, Kusumoto T, Kusumoto H, Anai H, Sugimachi K
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Chemotherapy. 1989;35(3):181-6. doi: 10.1159/000238668.
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.
采用体外琥珀酸脱氢酶抑制试验，测定了33例人肿瘤组织（11例胃癌、6例结直肠癌和16例恶性淋巴瘤）对1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷）和阿糖胞苷的一种掩蔽化合物N4-山嵛酰-1-β-D-阿拉伯呋喃糖基胞嘧啶（BH-AC）的敏感性。将肿瘤组织暴露于8.8或88微摩尔的药物中3天后，测定其琥珀酸脱氢酶（SD）活性，当SD活性降至88微摩尔时对照细胞活性的50%以下时，敏感性被认为呈阳性。在8.8微摩尔时SD活性降低很少，在88微摩尔时个别降低。在胃肠道癌中，88微摩尔时阿糖胞苷的SD活性平均值为65.7±11.5%，BH-AC为61.4±14.5%；在恶性淋巴瘤中，阿糖胞苷为63.8±16.0%，BH-AC为58.3±18.3%，差异有统计学意义（p＜0.05）。BH-AC转化为阿糖胞苷以发挥细胞毒性作用，阿糖胞苷和BH-AC的SD活性之间存在正相关（88微摩尔时r = 0.825）。化学敏感性因组织而异，18%的组织对阿糖胞苷敏感，27%对BH-AC敏感，15%对BH-AC敏感但对阿糖胞苷耐药。我们的研究结果表明，阿糖胞苷和BH-AC对人类肿瘤具有同等的细胞生长抑制作用。阿糖胞苷和BH-AC的敏感性试验能够确定哪种药物最适合个体患者。
