Sister chromatid exchange induction by diaziquone in human and mouse lymphocytes following both in vivo and in vitro exposures.
Diaziquone (AZQ) (NSC 182986), a lipid-soluble benzoquinone derivative currently being tested as an experimental chemotherapeutic agent, was used to treat mouse and human peripheral blood lymphocytes (PBLs) to determine its genotoxic potential by examination of sister chromatid exchange (SCE) induction. In vitro exposure to AZQ caused a linear increase in SCE in both mouse and human PBLs, with mouse PBLs being about twice as sensitive as the human cells. The lowest in vitro concentration found to induce a significant effect on SCE frequency was 0.3 micrograms/ml in mice and 1.0 micrograms/ml in human PBLs. Mice exposed by either i.p. or i.v. injection showed similar dose-related linear increases in SCE frequencies in their PBLs. After i.v. administration of AZQ, splenocytes from treated mice showed approximately the same SCE frequency as found in the PBLs. In general, AZQ caused a slowing of cell cycling in vivo while giving inconsistent responses in vitro. AZQ did cause a dose-related decrease in the number of recoverable mononuclear lymphocytes in mice treated in vivo. Contrary to the in vitro studies, comparison of SCE responses in mice with those previously observed in brain tumor patients undergoing chemotherapy with AZQ (Kligerman et al., Cancer Res., 47: 631-635, 1987) revealed AZQ was a much more potent SCE inducer in humans than in mice.
Kligerman
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Environmental Health Research and Testing, Inc., Research Triangle Park, North Carolina 27709.
Erexson
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Bryant
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D016227:Benzoquinones; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013045:Species Specificity
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D004247:DNA; C029108:diaziquone