INTERACTION OF TOPOISOMERASE-I INHIBITORS WITH RADIATION IN CIS-DIAMMINEDICHLOROPLATINUM(II)-SENSITIVE AND CIS-DIAMMINEDICHLOROPLATINUM(II)-RESISTANT CELLS-INVITRO AND IN THE FSAIIC FIBROSARCOMA INVIVO

被引:54
作者
BOSCIA, RE
KORBUT, T
HOLDEN, SA
ARA, G
TEICHER, BA
机构
[1] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115
[2] JOINT CTR RADIAT THERAPY,BOSTON,MA 02115
[3] MED UNIV S CAROLINA,CHARLESTON,SC 29425
关键词
D O I
10.1002/ijc.2910530122
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The cytotoxicity of the topoisomerase-I inhibitors, camptothecin and topotecan, toward the SCC-25 human head-and-neck squamous-carcinoma cells and the SCC-25/CDDP sub-line made resistant to cis-diamminedichloroplatinum(II) was assessed alone and in combination with radiation. Topotecan was less cytotoxic than camptothecin in cell culture and the SCC-25/CDDP cell line was more sensitive to either topoisomerase-I inhibitor than was the parental SCC-25 cell line. Both camptothecin and topotecan were effective radiation sensitizers of hypoxic SCC-25 and SCC-25/CDDP cells under normal pH or acidic pH conditions. Sensitizer-enhancement ratios ranged between 1.5 and 1.6 for hypoxic SCC-25 cells and between 1.3 and 1.5 for hypoxic SCC-25/CDDP cells. When the ability of campothecin or topotecan to sensitize the FSaIIC fibrosarcoma to single-dose radiation was assessed using the tumor-cell-survival assay, a sensitizer-enhancement ratio of 1.2 was found with each drug. However, using tumor growth delay of the FSaIIC fibrosarcoma to determine the effect of camptothecin or topotecan to enhance the efficacy of a daily fractionated radiation regimen, topotecan produced a sensitizer-enhancement ratio of 1.4, while that for camptothecin was 1.2. These results indicate that topoisomerase-I inhibitors may retain activity in CDDP-resistant cells and may be effective adjuncts to radiation therapy.
引用
收藏
页码:118 / 123
页数:6
相关论文
共 22 条
  • [1] BOOTHMAN DA, 1989, CANCER RES, V49, P605
  • [2] NOVOBIOCIN ENHANCES ALKYLATING AGENT CYTOTOXICITY AND DNA INTERSTRAND CROSS-LINKS IN A MURINE MODEL
    EDER, JP
    TEICHER, BA
    HOLDEN, SA
    CATHCART, KNS
    SCHNIPPER, LE
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (05) : 1524 - 1528
  • [3] ENG WK, 1988, MOL PHARMACOL, V34, P755
  • [4] ALKYLATING AGENT RESISTANCE - INVITRO STUDIES WITH HUMAN CELL-LINES
    FREI, E
    CUCCHI, CA
    ROSOWSKY, A
    TANTRAVAHI, R
    BERNAL, S
    ERVIN, TJ
    RUPRECHT, RM
    HASELTINE, WA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (07) : 2158 - 2162
  • [5] COMPARISON OF EFFECTS OF FOSTRIECIN, NOVOBIOCIN, AND CAMPTOTHECIN, INHIBITORS OF DNA TOPOISOMERASES, ON DNA-REPLICATION AND REPAIR IN HUMAN-CELLS
    GEDIK, CM
    COLLINS, AR
    [J]. NUCLEIC ACIDS RESEARCH, 1990, 18 (04) : 1007 - 1013
  • [6] HALL EJ, 1978, RADIOBIOLOGY RADIOLO, P129
  • [7] HERMAN TS, 1989, CANCER RES, V49, P3338
  • [8] HERMAN TS, 1988, CANCER RES, V48, P2342
  • [9] HERMAN TS, 1988, CANCER RES, V48, P2335
  • [10] OVEREXPRESSION OF METALLOTHIONEIN CONFERS RESISTANCE TO ANTICANCER DRUGS
    KELLEY, SL
    BASU, A
    TEICHER, BA
    HACKER, MP
    HAMER, DH
    LAZO, JS
    [J]. SCIENCE, 1988, 241 (4874) : 1813 - 1815