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Induction of Chromosome Breaks in Cultured Normal Human Leukocytes by Potassium Arsenite, Hydroxyurea and Related Compounds

( Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, and Department of Pediatric Research, University of Maryland Hospital, Baltimore, Maryland)

Hydroxyurea and N-hydroxyurethane at mM concentrations produced a high incidence of chromosome breaks along with other signs of cell toxicity in short-term cultures of phytohemagglutinin-stimulated normal human leukocytes. Chromosome rearrangements as well as breaks were produced by µM levels of potassium arsenite, suggesting that interference with oxidative phosphorylation can result in chromosome fragmentation. Acetohydroxamic acid and hydroxylamine both resulted in signs of cell injury but no significant chromosomal damage at µM concentrations. Urea, although inactive at physiologic concentrations, at 50 mM produced marked chromosomal fragmentation and evidence of cytoxicity.

Received 1/29/65.