Sodium arsenite-induced chromosomal aberrations in the Xq arm of Chinese hamster cell lines.

摘要

Non-cytotoxic concentrations (1.5, 3 and 6 microM) of sodium arsenite (SA) were used to study its cytogenetic effects with special reference to the frequency and nature of chromosomal aberrations on the X chromosome at Xq21 and at centromeric regions in CHO9, EM-C11, V79, V-H4 and CHE cell lines using Giemsa and FISH techniques. A high frequency of chromosomal breakpoints was distributed on the X chromosome localized at the secondary constriction region of the q arm (Xq21) and to a lesser degree at the centromeric region (c band-positive region), showing a high degree of fragility of these regions. This phenomenon was observed in all cell lines except for V79, where aberrations were localized only in the Xq21 region, and CHO9, where the observed breakage frequency was lowest in comparison with other cell lines and breaks were mostly located in the centromeric region rather than at Xq21. Homozygous expression of the breakpoint at Xq21 (fragile site) and in the centromeric region was also confirmed using a female Chinese hamster embryonic (CHE) cell line, which showed a similar high frequency of breakpoints at Xq21 and in the centromeric region of both X chromosomes. Further, a detailed cytogenetic study in CHO9 and its ligase-deficient mutant EM-C11 cell line showed slightly higher sensitivity to SA in a cell survival assay. No difference was found for chromosomal aberrations in Giemsa stained preparations. For SCEs a higher spontaneous frequency was evident in EMC-11. SA significantly increased the frequency of SCEs in CHO9, but no effect was found in EM-C11. Further, we observed an increased number of abnormal cells with pulverised chromosomes, decondensed chromatin, isochromosomes and hyperploidy in CHO9 and EM-C11 cell lines at all doses of SA.