Sister chromatid exchange in human lymphocytes exposed to ascorbic acid and the cancer chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.
This study examines sister chromatid exchange (SCE) induction by ascorbate, a weak in vitro SCE inducer which acts through free radical intermediates, and low doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), a potent SCE inducer which acts primarily through DNA interstrand cross-links. A small dose-dependent increase in SCE was observed in human peripheral lymphocytes exposed to ascorbate in the 0.5-10 mM dose range for 59 hours, with significant slowing of cell cycle kinetics at concentrations at and above 5 mM. CCNU concentration was selected to approximate the maximal increase in SCE induced by ascorbate. SCE frequencies in cells exposed sequentially to both agents were not significantly different from expectations under an additivity-of-effect model based on SCE response to each agent individually. Despite clear differences in the types of lesions induced, ascorbate and CCNU appear to act independently to induce SCE in a manner consistent with, though not exclusive to, Painter's replicon cluster model.
Best
R G
RG
Department OB/GYN, University of South Carolina School of Medicine, Columbia.
McKenzie
W H
WH
D000328:Adult; D001205:Ascorbic Acid / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D008130:Lomustine / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D008130:Lomustine; D001205:Ascorbic Acid