Antioxidant activity of diphenyl diselenide prevents the genotoxicity of several mutagens in Chinese hamster V79 cells.
Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. Studies have shown its antioxidant, hepatoprotective, neuroprotective, anti-inflammatory, and antinociceptive effects. We recently showed the antioxidant effect of DPDS in V79 cells, and established the beneficial and toxic doses of this compound in this cell line. Here, we report the antigenotoxic and antimutagenic properties of DPDS, investigated by using a permanent lung fibroblast cell line derived from Chinese hamsters. We determined the cytotoxicity by clonal survival assay, and evaluated DNA damage in response to several mutagens by comet assay and micronucleus test in binucleated cells. In the clonal survival assay, at concentrations ranging from 1.62 to 12.5microM, DPDS was not cytotoxic, while at concentrations up to 25microM, it significantly decreased survival. The treatment with this organoselenium compound at non-cytotoxic dose range increased cell survival after challenge with hydrogen peroxide, methyl-methanesulphonate, and UVC radiation, but did not protect against 8-methoxypsoralen plus UVA-induced cytotoxicity. In addition, the treatment prevented induced DNA damage, as verified in the comet assay. The mutagenic effect of these genotoxins, as measured by the micronucleus test, similarly attenuated or prevented cytotoxicity and DNA damage. Treatment with DPDS also decreased lipid peroxidation levels after exposure to hydrogen peroxide MMS, and UVC radiation, and increased glutathione peroxidase activity in the extracts. Our results clearly demonstrate that DPDS at low concentrations presents antimutagenic properties, which are most probably due to its antioxidant properties.
Rosa
Renato Moreira
RM
Departamento de Biofísica e Centro de Biotecnologia, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Moura
Dinara Jaqueline
DJ
Romano E Silva
Ana Catarina
AC
Saffi
Jenifer
J
Pêgas Henriques
João Antonio
JA
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000633:toxicity; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011701:PUVA Therapy / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
D016587:Antimutagenic Agents; D000975:Antioxidants; D001555:Benzene Derivatives; D009153:Mutagens; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase