This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shen, C.-L. Articles by Pence, B. C. Search for Related Content PubMed PubMed Citation Articles by Shen, C.-L. Articles by Pence, B. C.

Interactions of Selenium Compounds with Other Antioxidants in DNA Damage and Apoptosis in Human Normal Keratinocytes¹

Texas Tech University Health Sciences Center, Lubbock, Texas 79430

Selenite (SeL) or selenomethionine (SeM) are the most common selenium (Se) compounds taken as dietary antioxidants to reduce oxidative stress. Because the public may frequently supplement Se compounds at high doses, the possible pro-oxidant effect of Se becomes a concern. SeL and SeM have entirely different pharmacokinetic effects based on dose-related cytotoxicity. Our laboratory has shown previously that high doses of SeL resulted in cytotoxicity and induction of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of primary human keratinocytes (NHK), compared with those treated with the same doses of SeM. Besides Se compounds, other dietary antioxidants, such as vitamin (Vit) C or Vit E, are often supplemented and taken together with Se compounds. However, the cellular effects of these interactions of Se with antioxidants are still unknown. In addition, copper is commonly present in drinking water, food, soil, or the environment to increase the possibility of subchronic toxicity. Copper has been shown to inhibit SeL-induced cytotoxicity and apoptosis in human colonic carcinoma cells. The present study was designed to investigate the interactive effects of SeL or SeM plus Vit C, trolox (a water-soluble Vit E), or copper sulfate (CuSO₄) on cell viability and induction of 8-OHdG adduct formation in DNA of NHK. NHK cells were treated with no Se, SeL (126.6 µM Se), or SeM (316.6 µM Se) plus two doses each of Vit C (2.27 and 4.45 µM), trolox (40 and 80 µM), or CuSO₄ (7.85 and 15.7 µM) for 24 h. Coincubation of Vit C or CuSO₄ with SeL appeared to protect NHK against SeL-induced cytotoxicity. However, synergistic effects were observed between SeL and trolox resulting in enhanced cytotoxicity. On the other hand, SeM + Vit C, SeM + trolox, and SeM + CuSO₄ did not affect cell viability. In the absence of Se supplementation, Vit C, trolox, or CuSO₄ alone did not induce 8-OHdG adduct formation, regardless of dose. When NHK cells were coincubated with SeL (126.6 µM Se) and Vit C or CuSO₄, they protected NHK from SeL-induced DNA damage with a reduction in 8-OHdG generation. In contrast, treatment of SeL + trolox elevated generation of 8-OHdG. Furthermore, treatments of SeM plus trolox or CuSO₄ elevated 8-OHdG adduct formation. In terms of apoptosis measured as internucleosomal DNA fragmentation, copper protected NHK against SeL-induced apoptosis in cultured NHK. These data suggest that the use of CuSO₄ may play a protective role in SeL-induced cytotoxicity, DNA oxidative damage, and apoptosis and that there may be potentially deleterious interactions among common high-dose antioxidant supplements taken by the public.

This article has been cited by other articles:

				M. El-Gohary, A.-E. Yassin, and M. A Shalabya The effect of chronic lead exposure on the course of schistosomiasis in hamsters and the protective effect of the antioxidant preparation 'Antox' Human and Experimental Toxicology, September 1, 2003; 22(9): 481 - 490. [Abstract] [PDF]

				H. E. Seifried, S. S. McDonald, D. E. Anderson, P. Greenwald, and J. A. Milner The Antioxidant Conundrum in Cancer Cancer Res., August 1, 2003; 63(15): 4295 - 4298. [Abstract] [Full Text] [PDF]

				A. E. Connelly, J. Satia-Abouta, C. F. Martin, T. O. Keku, J. T. Woosley, P. K. Lund, and R. S. Sandler Vitamin C Intake and Apoptosis in Normal Rectal Epithelium Cancer Epidemiol. Biomarkers Prev., June 1, 2003; 12(6): 559 - 565. [Abstract] [Full Text] [PDF]