Record Display for the EPA National Library Catalog


Main Title Genotoxicity of Inhibitors of DNA Topoisomerases I (Camptothecin) and II (m-AMSA) In vivo and In vitro.
Author Backer, L. C. ; Allen, J. W. ; Harrington-Brock, K. ; Campbell, J. A. ; DeMarini, D. M. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.
Publisher c1990
Year Published 1990
Report Number EPA/600/J-90/421;
Stock Number PB91-171769
Additional Subjects Enzyme inhibitors ; Mutagens ; Camptothecin ; Amsacrine ; DNA topoisomerase I ; DNA damage ; Mutagenicity tests ; In vitro analysis ; In vivo analysis ; Lymphoma ; Chromosome aberrations ; Cell cycle ; Thymidine linase ; Cultured tumor cells ; Adenosine cyclic monophosphate ; Reprints ;
Library Call Number Additional Info Location Last
NTIS  PB91-171769 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 9p
The present study was designed to determine and compare the clastogenicity of amsacrine and camptothecin in vivo in mouse bone marrow and peripheral blood lymphocytes and in vitro in mouse lymphoma L5178Y cells. It was expected that amsacrine, which interferes with topoisomerase II to induce double-strand DNA breaks, and camptothecin, which interferes with topoisomerase I to induce single-strand DNA breaks, would induce different types of chromosomal aberrations. However, both drugs produced quantitatively and qualitatively similar numbers and types of aberrations under similar experimental conditions. In mouse bone marrow, both drugs (3 mg/kg) induced about 30% damaged cells, with an average of 0.4 chromatid breaks per cell. Cell cycle specificity was indicated by the absence of chromosomal aberrations when exposure to the drugs occurred during GO in vivo. In vitro, amsacrine, and camptothecin induced 161 and 20 mutants/10 (to the sixth power) survivors/nM, respectively; they induced 6 and 2 aberrant cells/nM, respectively. In contrast to the in vivo results, the drugs induced high levels of both chromatid- and chromosome-type aberrations in vitro.