Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line.
In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1muM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified.
Hornhardt
Sabine
S
BfS-Federal Office for Radiation Protection, Department of Radiation Protection and Health, Ingolstädter Landstr. 1, 85764 Oberschleissheim, Germany. shornhardt@bfs.de
Gomolka
Maria
M
Walsh
Linda
L
Jung
Thomas
T
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000077237:Arsenic Trioxide; D001152:Arsenicals; D018053:Arsenites / Q000633:toxicity*; D019187:Cadmium Compounds / Q000633:toxicity*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D015162:Micronucleus Tests; D010087:Oxides / Q000633:toxicity*; D017670:Sodium Compounds / Q000633:toxicity*; D013431:Sulfates / Q000633:toxicity*
D001152:Arsenicals; D018053:Arsenites; D019187:Cadmium Compounds; D010087:Oxides; D017670:Sodium Compounds; D013431:Sulfates; C017947:sodium arsenite; C037123:cadmium sulfate; D000077237:Arsenic Trioxide