title: Influence of novel naphthalimide-based organoselenium on genotoxicity induced by an alkylating agent: the role of reactive oxygen species and selenoenzymes.
abstract: OBJECTIVE
  The protection conferred by a series of synthetic organoselenium compounds against genotoxicity and oxidative stress induced by a reference mutagen cyclophosphamide (CP) was assessed.
  
  
  METHODS
  Genotoxicity was induced in mice by CP treatment (25 mg/kg b.w.) for 10 consecutive days. Organoselenium compounds (3 mg/kg b.w.) were administered orally in a concomitant and pretreatment schedule. DNA damage in peripheral blood lymphocytes and frequency of chromosomal aberration in the bone marrow cells were measured. Liver tissues were collected for analysis of the activity of antioxidant and detoxifying enzymes, lipid peroxidation (LPO) level, glutathione content, and histopathology.
  
  
  RESULTS
  Exposure to CP not only led to a significant increase in the percent of chromosomal aberration and DNA damage, but also enhanced generation of hepatic reactive oxygen species (ROS) and LPO level. The organoselenium compounds demonstrated marked functional protection against CP-induced genotoxicity. DNA damage and chromosomal aberration along with ROS generation were attenuated in the organoselenium-treated mice compared with the CP-treated control mice. CP caused marked depression in the activities of the selenoenzymes (glutathione peroxidase (GPx) and thioredoxin reductase (TRxR)) and other detoxifying and antioxidant enzymes, while treatment with organoselenium compounds restored all these activities towards normal.
  
  
  CONCLUSIONS
  The protective effect of these compounds may be primarily associated with the improvement of the activity of antioxidant and detoxifying enzymes (including the selenoenzymes, GPx, and TRxR) that are known to protect the DNA and other cellular components from oxidative damage.
authors.affiliation: Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Somnath Singha
authors.initials: SS
authors.lastname: Roy
authors.forename: Pramita
authors.initials: P
authors.lastname: Chakraborty
authors.forename: Prosenjit
authors.initials: P
authors.lastname: Ghosh
authors.forename: Sulekha
authors.initials: S
authors.lastname: Ghosh
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.forename: Sudin
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced; D020552:Comet Assay; D003520:Cyclophosphamide / Q000633:toxicity; D004249:DNA Damage; D004789:Enzyme Activation; D057075:Enzyme Assays; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009152:Mutagenicity Tests; D053644:Naphthalimides / Q000008:administration & dosage / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D016587:Antimutagenic Agents; D053644:Naphthalimides; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D003520:Cyclophosphamide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione