Title: Variability in sensitivity to arsenite does not correlate with arsenic accumulation rate in normal human lymphoblasts.
Authors: Li, Ping; Uddin, Ahmed N; Liu, Zijuan; Mukhopadhyay, Rita; Komissarova, Elena V; Rosen, Barry P; Rossman, Toby G
Published In Mol Cell Biochem, (2004 Jan)
Abstract: Arsenic is a common environmental contaminant of our air, water and food, but not every individual who drinks arsenic-contaminated water shows clinical signs of toxicity. Large inter-individual variations are also found in arsenite-induced aneuploidy, chromosome aberrations and sister chromatid exchanges in peripheral blood lymphocytes from different human donors. Lymphoblasts are virally immortalized lymphocytes that retain most of the properties of lymphocytes. Individual lymphoblast cell lines retained their arsenite sensitivity after cryopreservation and subsequent revival. We measured the accumulation of 73[As]-arsenite into lymphoblast lines derived from 11 normal individuals. Arsenite accumulation rate varied 6.3 fold between the slowest and the fastest subjects. Assays in 14 lymphoblast lines showed variability to the toxic effects of arsenite, as measured by growth inhibition. Lymphoblast lines also vary with regard to their growth rates, but there is no relationship between growth rate and arsenite sensitivity. Surprisingly, we also found no correlation between arsenite accumulation rate and cellular sensitivity to growth inhibition, suggesting that the arsenite accumulation rate may not be the main determinant of cellular sensitivity to arsenic. We were also unable to detect evidence for a human homolog for the yeast arsenite efflux gene ACR3, using RT-PCR.
PubMed ID: 14971648
MeSH Terms: Adolescent; Adult; Arsenites/metabolism; Arsenites/pharmacokinetics; Arsenites/toxicity*; Cell Line, Transformed; Child; Chromosome Aberrations/chemically induced; Drug Resistance/genetics; Genetic Variation; Humans; Lymphocytes/drug effects*; Lymphocytes/metabolism; Middle Aged; Sister Chromatid Exchange/physiology; Teratogens/metabolism; Teratogens/pharmacokinetics; Teratogens/toxicity*