Genotoxic effects of gossypol acetic acid on cultured murine erythroleukemia cells.
Gossypol acetic acid, a male anti-fertility drug, was evaluated for its effects on cell multiplication, chromosomes, scheduled and unscheduled DNA synthesis, and the surface ultrastructure in cultured murine erythroleukemia cells (clone 6A11A). Gossypol treatments inhibited cell multiplication at 10 and 20 micrograms/ml concentrations and this inhibitory effect increased with elevated dosage and prolonged treatment. Gossypol significantly depressed the mitotic index but did not alter chromosome numbers or increase the frequency of chromosomal structural abnormalities. Cell fraction techniques revealed that gossypol induced a negative effect on cellular DNA synthesis at concentrations as low as 3.3 micrograms/ml after 24 hr of treatment. The number of cells undergoing DNA synthesis decreased with increasing dosages and durations of drug exposure. An unscheduled DNA synthesis assay (UDS) found gossypol to be an active UDS-inducing agent at certain dose levels and treatment times, as measured by increase in net nuclear gain and percentage of UDS cells (ANOVA, Bonferroni test, P less than 0.05). A scanning electron microscope study revealed that 10 micrograms/ml treatment with gossypol caused changes in mouse erythroleukemia cell surface ultrastructure characterized by general balding and the appearance of holes, often after 48 hr of treatment.
Department of Biology, Lafayette College, Easton, PA 18042.
S K
SK
Majumdar
E P
EP
Daly
K M
KM
Kleemeyer
C C
CC
Daehler
M A
MA
Baker
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002869:Chromosome Aberrations; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D006072:Gossypol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008940:Mitotic Index / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D009153:Mutagens; D014316:Tritium; D006072:Gossypol; C028178:gossypol acetic acid; D013936:Thymidine