Hypoxia enhances the lethality of mitomycin C and carboquone against human malignant tumor cells in vitro

T. Kusumoto, Yoshihiko Maehara, Y. Sakaguchi, M. Saku, K. Sugimachi

Research output: Contribution to journalArticle

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Abstract

Solid tumors contain hypoxic cells which are relatively resistant to antineoplastic activity of radiation or to chemotherapeutic agents. We determined the increase in antineoplastic activities of mitomycin C (MMC) and carboquone (CQ) against human tumor cells under conditions of in vitro hypoxia, with the following results, (a) The HeLa cells had been exposed to various concentrations of MMC or CQ for 2 h under normally aerated (about 20%) or hypoxic conditions (5.0 and 0%) and were maintained under normally aerated conditions for 3 days. The succinate dehydrogenase activity was assayed, using the succinate dehydrogenase inhibiton (SDI) lest. Treatment with MMC or CQ reduced the SD activity, compared to findings in the control cells, under hypoxic conditions, (b) The cells were exposed to the drug, MMC or CQ, under normally aerated or anoxic conditions, for 15-45min and the colonies counted on day 14. Treatment with 0,45 μMof MMC for 45 min inhibited the clonogenicity of HeLa cells by 25.4% of findings in the control cells under anoxia. Treatment with 0.03 μM of CQ for 30 min inhibited the clonogenicity by 41.5%. (c)The sensitivity of 14 human tumor tissues (6 gastric and 8 colorectal cancers) to MMC or CQ under hypoxic conditions was determined, using the SDI test. MMC and CQ showed hypoxic enhancement. Therefore, MMC and CQ have definite positive effects on hypoxic cells, and hence a higher therapeutic ratio for treating clinical solid tumors.

Original languageEnglish
Pages (from-to)224-231
Number of pages8
JournalEuropean Surgical Research
Volume21
Issue number3-4
DOIs
Publication statusPublished - Jan 1 1989

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Carbazilquinone
Mitomycin
Succinate Dehydrogenase
Neoplasms
HeLa Cells
Antineoplastic Agents
Cell Hypoxia
Hypoxia
In Vitro Techniques
Colorectal Neoplasms
Stomach
Radiation

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Hypoxia enhances the lethality of mitomycin C and carboquone against human malignant tumor cells in vitro. / Kusumoto, T.; Maehara, Yoshihiko; Sakaguchi, Y.; Saku, M.; Sugimachi, K.

In: European Surgical Research, Vol. 21, No. 3-4, 01.01.1989, p. 224-231.

Research output: Contribution to journalArticle

Kusumoto, T. ; Maehara, Yoshihiko ; Sakaguchi, Y. ; Saku, M. ; Sugimachi, K. / Hypoxia enhances the lethality of mitomycin C and carboquone against human malignant tumor cells in vitro. In: European Surgical Research. 1989 ; Vol. 21, No. 3-4. pp. 224-231.
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