Abnormal DNA repair in selenium-treated human cells.
Selenium (Se), a micronutrient and an environmental, a chemical and an industrial agent in many products, can have genotoxic effects as well as antimutagenic and/or anticarcinogenic properties, depending on its concentration and oxidation state. We investigated the cytotoxic response of human osteosarcoma (U2OS) cells to low doses of sodium selenite and assayed their resistivity to cisplatin treatment and their capacity to reactivate cisplatin-treated reporter system, whose repair occurs through the transcription coupled repair (TCR) pathway, using the Host Cell Reactivation (HCR) Assay. In addition, we examined the ability of Se-treated human primary lymphocytes for normal double-strand breaks rejoining (DSBR) using the Challenge assay. Although, U2OS cells did not demonstrate cytotoxicity to all Se doses used, as measured by the cell proliferation MTT assay, their resistivity to cisplatin was significantly reduced. Moreover, Se-treated cells exhibited a significant reduction in their capacity for TCR as compared with untreated control cells. Primary human blood lymphocytes demonstrated cytotoxicity to Se treatment at only a concentration of 10 microM. There were no significant increases in chromosome-type deletions or chromatid breaks or in mitotic indices in cells treated with Se alone or Se plus ionizing irradiation. However, dicentric chromosomes significantly increased upon treatment with 1 microM Se plus irradiation as compared with Se-untreated irradiated control. These findings demonstrate direct evidence on the inhibitory effect of inorganic Se on cellular DNA repair capacity.
Abul-Hassan
Khaled S
KS
Basic Research Laboratory, National Cancer Institute, Building 37, Room 6144, NCI, National Institutes of Health, 37 Convent Dr MSC 4255, Bethesda, MD 20892-4255, USA. khaled_abul_hassan@hotmail.com
Lehnert
Bruce E
BE
Guant
Lorraine
L
Walmsley
Richard
R
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects*; D002869:Chromosome Aberrations / Q000139:chemically induced; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D012516:Osteosarcoma; D018038:Sodium Selenite / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D018038:Sodium Selenite; D002945:Cisplatin