title: Tumor and non-tumor tissues differential oxidative stress response to supplemental DHA and chemotherapy in rats.
abstract: OBJECTIVE
  Developing approaches that will increase the selectivity of anticancer drugs remains a challenge. Docosahexaenoic acid (DHA) has the potential to increase tumor sensitivity to chemotherapy with no sensitization of normal tissues. This study was aimed at exploring the mechanism involved in this differential sensitization with a focus on oxidative stress, one of the main determinants involved in DHA enhancement of anthracycline-based chemotherapy.
  
  
  METHODS
  In a previously validated model of chemically induced mammary tumors in rats where supplemental DHA sensitized tumors to epirubicin, DHA level, lipid hydroperoxides (LPO), total antioxidant activity, glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities were measured in tumors, intestine, liver, and heart in rats treated with DHA+epirubicin and in control rats (palm oil, no chemotherapy).
  
  
  RESULTS
  At baseline, the level of LPO was similar in tumors, liver, heart, and small intestine. The proportion of DHA was higher in non-tumor tissues compared to tumors (liver or heart, p < 0.0001; intestine, p = 0.01). DHA and epirubicin induced a significant increase in LPO in tumors (p = 0.03), but no increase was detected in liver, heart, or intestine. The difference in LPO production between these tissues was associated with differences in their antioxidant defenses. In tumors, the adjustment of GPx activity was possible but limited, and no adjustment of their total antioxidant and SOD activities was observed compared to other tissues.
  
  
  CONCLUSIONS
  Supplementing DHA during an anthracycline-based chemotherapy induced a selective increase of LPO in tumors. This selectivity might result from a differential handling of oxidative stress between tumor and non-tumor tissues.
authors.affiliation: Cancer Research Laboratory, University Hospital of Tours, Tours, France. n.hajjaji@chu-tours.fr
authors.forename: Nawale
authors.initials: N
authors.lastname: Hajjaji
authors.forename: Pierre
authors.initials: P
authors.lastname: Besson
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D015251:Epirubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008770:Methylnitrosourea; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D008054:Lipid Peroxides; D004281:Docosahexaenoic Acids; D015251:Epirubicin; D008770:Methylnitrosourea; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase