DNA damage produced by cadmium in a human fetal hepatic cell line

Cadmium (Cd) is one of the most important heavy metal environmental toxican ts. It alters a wide variety of cellular and biochemical processes. The obj ective of this work was to study DNA damage and recovery after acute and ch ronic CdCl2 treatment in a human fetal hepatic cell line (WRL-68 cells). Us ing the alkaline microgel electrophoresis assay that detects DNA single-str and breaks and/or alkali-labile sites in individual cells, we evaluated for levels of DNA damage. The mean migration length in control cells was 35.37 +/- 1.43 mu m (8% damaged cells), whereas the mean migration in cells trea ted with 0.005 mu M CdCl2 for 3 h (acute low dose) was 65.87 +/- 2.07 mu m (88% damaged cells). Treatment with 0.01 mu M CdCl2 for the same time (acut e high dose) increased the mean migration length to 125.79 +/- 2.91 mu m (9 2% damaged cells). However, a 0.005 mu M CdCl2 treatment for 7 days (chroni c treatment) only increased 65% DNA migration to 58.38 +/- 2.59 mu m (88% d amaged nucleus). Lipoperoxidative damage expressed as malondialdehyde (MDA) production per milligram of protein was 15.7 +/- 2.6 for control cells, wh ereas in Cd-treated cells the values were 20.2 +/- 2.4 (acute low dose), 22 .9 +/- 2.2 (acute high dose), and 22.6 +/- 2.1 (chronic treatment). To stud y the repair of DNA damage, cells were washed with 0.01 mu M meso-2,3-dimer captosuccinic acid (DMSA), and fresh Dulbecco's modified essential medium ( DMEM) added. The percentage of damaged cells diminished after 90 min, with DNA migration returning to control values by 120 min. Cd treatment produced DNA single-strand breaks and the damage was greater in acute high dose tre ated cells. Lipid peroxidation values did not correlate with DNA single-str and breaks. (C) 1999 Elsevier Science B.V. All rights reserved.