title: The genotoxic effects of anti-cancer drug gossypol on human lymphocytes and its mitigation by melatonin.
abstract: OBJECTIVE
  To determine melatonin as a potential natural antioxidant to mitigate the genotoxic effects of promising anti-cancer drug gossypol in human lymphocytes.
  
  
  BACKGROUND
  Gossypol, is a polyphenolic compound naturally occurring in cotton seed, was originally identified as a male contraceptive but it has several proposed clinical applications. Gossypol has anti-proliferative effects on cancer cell lines. However, its genotoxic effects on normal cells are not much studied. Hence, there is a paucity of data available. Hence, the study was conducted to investigate gossypol-induced genotoxic effects on lymphocytes.
  
  
  METHODS
  Peripheral blood lymphocyte cultures (PBLC) were done and exposed by two different doses of an anti-cancer drug, gossypol (0.274 mM, 1.645 mM) to check genotoxic effects. Melatonin (0.2 mM) is used as an antioxidant. Genotoxic indices such as sister chromatid exchanges (SCEs), cell cycle proliferative index (CCPI), average generation time (AGT), population doubling time (PDT) were assayed in the cultures.
  
  
  RESULTS
  Gossypol-treated groups indicated significant increases in frequency of SCEs calculated for SCE/plate and SCE/chromosome. Furthermore, CCPI showed a remarkable reduction and increased AGT and PDT levels were found in exposed cultures. When the higher dose of gossypol cultures was treated along with melatonin, these indices were found to be declined and comparable to control.
  
  
  CONCLUSIONS
  Gossypol, an anti-cancer drug, induces genotoxicity on lymphocyte cells and co-supplementation of melatonin antioxidant ameliorates these toxic effects of gossypol.
authors.affiliation: a Human Genetics Division, Department of Zoology , BMTC and HG, School of Sciences, Gujarat University , Ahmedabad , Gujarat , India.
authors.forename: Mandava Venkatesh
authors.initials: MV
authors.lastname: Rao
authors.affiliation: a Human Genetics Division, Department of Zoology , BMTC and HG, School of Sciences, Gujarat University , Ahmedabad , Gujarat , India.
authors.forename: Moksha B
authors.initials: MB
authors.lastname: Narechania
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D018929:Cell Culture Techniques; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006072:Gossypol / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D009153:Mutagens; D008550:Melatonin; D006072:Gossypol
keywords: Anti-cancer drug; SCEs; genotoxicity; gossypol; melatonin