Variation in arsenic-induced sister chromatid exchange in human lymphocytes and lymphoblastoid cell lines

Abstract

This study was undertaken to compare the genotoxic effects of arsenite in cultured human lymphocytes and lymphoblastoid cell lines from a group of normal human volunteers. The goal was to determine whether, as found with other genotoxins, subgroups might exist which showed relative high or low sensitivity to induction of sister chromatid exchanges (SCEs) by this metal. Primary lymphoblast cultures were established by treatment with phytohemagglutinin (PHA-L). Lymphoblastoid cell lines were established by transformation with Epstein-Barr virus. Cultures were exposed for 40 h to sodium arsenite (AsIII) and SCEs assayed by 5-bromo-2'-deoxyuridine incorporation and staining by fluorescence plus Giemsa. SCEs were increased by arsenite in a dose-dependent manner over the concentration range of 10(-7)-10(-5) M. SCEs could not be scored above 10(-5) M because of cytotoxicity. Comparison of SCE frequency in primary lymphocyte cultures among individuals showed substantial variation in sensitivity to arsenite, with some showing no significant effect while others showed a 2-3-fold increase in SCE frequency. In one lymphoblastoid cell line especially sensitive to arsenite, arsenic acid (AsV) or dimethylarsinic acid (DMA) at concentrations up to 10(-5) M did not increase the SCE frequency suggesting that AsIII is the active form of arsenic. When pooled data from the primary lymphocytes was compared to that obtained with the lymphoblastoid cells, the slopes of the dose-response curves for ASIII-induced SCEs were similar. The sensitivity of the majority of the individual primary lymphocyte cultures to SCE induction by arsenite was correlated with the sensitivity of the lymphoblastoid cultures established from the same individual. However, in three individuals no correlation was found. Individual lymphoblastoid cell lines retained their As sensitivity after cryopreservation and subsequent revival. Whether the genotoxic response to As is genetically controlled or the result of phenotypic selection is being explored in these stable lymphoblastoid cell lines.