Loss in cell killing effectiveness of anticancer drugs in human gastric cancer clones due to recovery from potentially lethal damage in vitro.
The ability of human gastric cancer clones to recover from potentially lethal damage was studied. Recovery was greatest following treatments with bleomycin or Adriamycin; the recovery ratios (i.e., survival) increased almost 8-fold during a posttreatment incubation period. Recovery was also possible following treatments with actinomycin D, 1,2:5,6-dianhydrogalactitol, and diaziquone; however, the recovery ratios never increased above 2. No recovery was observed following treatment with 5-fluorouracil. Recovery from potentially lethal damage may be related to the heterogeneity in survival responses observed following treatment with some anticancer drugs. Bleomycin and Adriamycin treatments result in large heterogeneous survival fractions among these human stomach cancer clones, and the potentially lethal damage recovery ratios were larger (and variable). However, actinomycin D, diaziquone, and 1,2:5,6-dianhydrogalacticol produce very uniform killing effects in these cells and the recovery ratios are very much smaller and less variable. Finally the large amount of recovery observed after bleomycin or Adriamycin treatments resulted in the loss of cell killing effectiveness of the agents. Because the survival fractions increased during the recovery period, the net effect on cell killing was reduced to an amount normally obtained with doses that were up to six times smaller.
Barranco
S C
SC
Townsend
C M
CM
D000970:Antineoplastic Agents / Q000633:toxicity*; D001388:Aziridines / Q000633:toxicity; D016227:Benzoquinones; D001761:Bleomycin / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003609:Dactinomycin / Q000633:toxicity; D003961:Dianhydrogalactitol / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D013274:Stomach Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D001761:Bleomycin; D003609:Dactinomycin; D003961:Dianhydrogalactitol; D004317:Doxorubicin; C029108:diaziquone; D005472:Fluorouracil