dicumarol and 2-(bis(2-hydroxyethyl)amino)-1-4-benzoquinone

dicumarol has been researched along with 2-(bis(2-hydroxyethyl)amino)-1-4-benzoquinone* in 2 studies

Other Studies

2 other study(ies) available for dicumarol and 2-(bis(2-hydroxyethyl)amino)-1-4-benzoquinone

ArticleYear
Activity of quinone alkylating agents in quinone-resistant cells.
    Cancer research, 1990, May-15, Volume: 50, Issue:10

    The role of the quinone group in the antitumor activity of quinone alkylating agents, such as mitomycin C and 2,5-diaziridinyl-3,5-bis(carboethoxyamino)-1,4-benzoquinone, is still uncertain. The quinone group may contribute to antitumor activity by inducing DNA strand breaks through the formation of free radicals and/or by influencing the alkylating activity of the quinone alkylators. The cytotoxic activity and DNA damage produced by the model quinone alkylating agents, benzoquinone mustard and benzoquinone dimustard, were compared in L5178Y murine lymphoblasts sensitive and resistant to the model quinone antitumor agent, hydrolyzed benzoquinone mustard. The resistant cell lines, L5178Y/HBM2 and L5178Y/HBM10, have increased concentrations of glutathione and elevated catalase, superoxide dismutase, glutathione S-transferase, and DT-diaphorase activity. L5178Y/HBM2 and L5178Y/HBM10 cells were 7.4- and 8.5-fold less sensitive to benzoquinone mustard and 1.7- and 4.3-fold less sensitive to benzoquinone dimustard, respectively, compared with sensitive cells, but showed no resistance to the non-quinone alkylating agent, aniline mustard. The formation of DNA double strand breaks by benzoquinone mustard was reduced by 2- and 8-fold in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, while double strand break formation by benzoquinone dimustard was reduced only in the L5178Y/HBM10 cells. The number of DNA-DNA cross-links produced by benzoquinone mustard was 3- and 6-fold lower, and the number produced by benzoquinone dimustard was 35% and 2-fold lower in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, compared with L5178Y parental cells. In contrast, cross-linking by aniline mustard was unchanged in sensitive and resistant cells. Dicoumarol, an inhibitor of DT-diaphorase, increased the cytotoxic activity of both benzoquinone mustard and benzoquinone dimustard in L5178Y/HBM10 cells. This study provides evidence that elevated DT-diaphorase activity in the resistant cells contributes to resistance to benzoquinone mustard and benzoquinone dimustard, possibly by decreasing the formation of the semiquinone intermediates of these agents. The altered reduction of the quinone groups in the resistant cells may be responsible for the decreased DNA-DNA cross-linking and lowered induction of DNA strand breaks by the quinone alkylating agents. These findings demonstrate that the quinone group can modulate the activity of quinone alkylating agents. The study also suggests tha

    Topics: Alkylating Agents; Alkylation; Animals; Benzoquinones; Biotransformation; Cell Line; Cell Survival; Cytotoxins; Dicumarol; DNA; DNA Damage; Drug Resistance; In Vitro Techniques; Leukemia L5178; Mice; Quinones

1990
Increased sensitivity of quinone resistant cells to mitomycin C.
    Cancer letters, 1989, Volume: 45, Issue:3

    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.

    Topics: Animals; Antineoplastic Agents; Benzoquinones; Cell Line; Cell Survival; Dicumarol; DNA Damage; Drug Resistance; Leukemia L5178; Leukemia, Experimental; Mice; Mitomycin; Mitomycins; NAD(P)H Dehydrogenase (Quinone); Quinone Reductases; Quinones; Tumor Cells, Cultured

1989
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