Increased sensitivity of quinone resistant cells to mitomycin C

Cancer Lett. 1989 Jun;45(3):173-6. doi: 10.1016/0304-3835(89)90073-6.

Abstract

L5178Y cells resistant to the model quinone antitumor agent, hydrolyzed benzoquinone mustard, were four-fold more sensitive to mitomycin C compared to parental cells. Mitomycin C also produced increased DNA-DNA crosslinking in these cells compared to parental L5178Y cells, but did not induce DNA double strand breaks in either cell line. The resistant cells have a 24-fold increased level of DT-diaphorase activity, an enzyme that produces two electron reduction of quinone groups. Dicoumarol, an inhibitor of DT-diaphorase, significantly inhibited crosslinking and cytotoxicity by mitomycin C in the quinone resistant cells. These findings suggest that DNA-DNA cross-linking may be a major contributor to mitomycin C cytotoxic activity in L5178Y cells, and that the hydroquinone of mitomycin C may play a major role in the crosslinking activity of this agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Benzoquinones*
  • Cell Line
  • Cell Survival / drug effects
  • DNA Damage
  • Dicumarol / pharmacology
  • Drug Resistance / genetics
  • Leukemia L5178 / genetics
  • Leukemia L5178 / metabolism*
  • Leukemia, Experimental / metabolism*
  • Mice
  • Mitomycin
  • Mitomycins / pharmacology*
  • NAD(P)H Dehydrogenase (Quinone)
  • Quinone Reductases / antagonists & inhibitors
  • Quinones / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Mitomycins
  • Quinones
  • 2-(bis(2-hydroxyethyl)amino)-1,4-benzoquinone
  • Mitomycin
  • Dicumarol
  • NAD(P)H Dehydrogenase (Quinone)
  • Quinone Reductases