PMID: 9639674Jun 26, 1998Paper

DNA damage and cytotoxicity induced by beta-lapachone: relation to poly(ADP-ribose) polymerase inhibition

Mutation Research
A VanniF Degrassi

Abstract

beta-Lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5, 6-dione) was previously shown to enhance the lethality of X-rays and radiomimetic agents and its radiosensitizing role in mammalian cells was attributed to a possible interference with topoisomerase I activity. Furthermore, beta-lapachone alone was found to induce chromosomal damage in Chinese hamster ovary (CHO) cells. The aim of the present study was to further elucidate the possible mechanisms by which beta-lapachone exerts its genotoxic action in cultured mammalian cells. Flow cytometry analysis of beta-lapachone-treated CHO cells indicated a selective cytotoxic effect upon S phase of the cell cycle. beta-lapachone produced DNA strand breaks as determined by alkaline elution assay; alkaline elution profiles from treated cells showed a bimodal dose-response pattern, with a threshold dose above which a massive dose-independent DNA degradation was observed. Furthermore, beta-lapachone increased the capacity of crude CHO cellular extracts to unwind supercoiled plasmid DNA, while significantly inhibiting in vitro poly(ADP-ribose) polymerase (PARP). These results suggest that damage induction is probably mediated by the interaction between beta-lapachone and cellu...Continue Reading

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Citations

Jan 20, 2012·Applied Biochemistry and Biotechnology·S ShuklaPankaj Kumar
Jun 23, 2001·Molecular and Biochemical Parasitology·S F VillamilA Stoppani
Aug 13, 2011·Chemical Research in Toxicology·Bruno C CavalcantiCláudia Pessoa
Sep 12, 2009·Chemico-biological Interactions·Igal ElingoldMarta Dubin
Jul 19, 2016·The Journal of Special Education·Ashley A ChesmoreArthur J Reynolds
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Feb 22, 2000·The Journal of Biological Chemistry·J J PinkD A Boothman
Nov 7, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Steven M BryceStephen D Dertinger
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Mar 7, 2021·Pathogens·Congrui ZhuPhilip R Hardwidge
Mar 29, 2021·Redox Biology·David Ross, David Siegel

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