Sister chromatid exchange induction near the baseline with low doses of the alkylating agent ccnu

Abstract

Sister chromatid exchange (SCE) and cell-cycle kinetics were examined at nearbaseline levels in human peripheral lymphocytes exposed to low doses of the potent SCE inducer 1 -(2-chloroethyl)-3-cyclohexyl-1 -nitrosourea (CCNU), in vitro. A preliminary SCE dose-response curve was determined with a broad range of doses of CCNU using a single donor. SCE induction was approximately linear over the entire dose range from 5 to 200 p M CCNU. Cell cycle kinetics were retarded in a dose-dependent manner. A second dose-response curve from the same donor was constructed using several doses of CCNU between 0.5 and 10 p M to evaluate linearity and uniformity of SCE response near baseline levels. SCE induction was approximately linear between 1.0 and 10.0 p M CCNU. Finally, SCE and cell-cycle kinetics were examined in 12 donors at doses of 1 .O, 5.0, and 10.0 p M CCNU to evaluate the reproducibility of near-baseline SCE induction over a range of subjects. Cell-cycle kinetics were retarded at all three doses with a highly significant increase in SCE frequencies at 5.0 and 10.0 pM CCNU. These data suggest that increases in SCE less than twice background can be reliable indicators of genotoxic exposure.