title: Dynamics of changes of antioxidant system indexes during the growth of two Lewis lung carcinoma variants.
abstract: OBJECTIVE
  To study an intensity of prooxidant processes and activity of antioxidant enzymes in tumor tissue of two Lewis lung carcinoma variants (LLC and LLC/R9) differing by their proliferative, metastatic, and angiogenic potential (LLC/R9 as compared to LLC is characterized by lower metastatic activity, higher proliferative and angiogenic potential).
  
  
  METHODS
  The in vitro study was carried out using cultured LLC and LLC/R9 cell lines, and in vivo on 50 female С57/BL6 mice. The indexes of prooxidant processes and activity of antioxidant enzymes have been studied using the methods of experimental oncology, optical spectroscopy, fluorescent spectroscopy, electron paramagnetic resonance, statistical analysis.
  
  
  RESULTS
  There has been determined the coherence of results on 1.5 fold higher (p < 0.01) level of spontaneous generation of reactive oxygen species (ROS) by LLC cells in vitro compared to LLC/R9 cells, and twice (p < 0.05) higher content of secondary products of lipid peroxidation at 14(th) and 17(th) day of tumor growth in LLC compared to that in LLC/R9. It has been shown that deficiency of nutrient substrates determines an increase (p < 0.01) of ROS production in LLC/R9 cells what is in congruence with the data on accumulation of nitrosyl complexes of heme iron in mitochondria of LLC/R9 during tumor growth. Activity of superoxide dismutase during tumor growth has altered in unmonotonous way: starting from 14(th) day of growth it sharply increased by 147% (17(th) day, LLC) and 217% (20(th) day, LLC/R9), and then decreased to the level registered at 14(th) day. Progressive decrease of activity of glutathione peroxidase (GP) and glutathione-S-transferase (GST) during LLC growth has been accompanied with the decrease of the level of reduced glutathione (GSH) by 70% (p < 0.05). In the case of LLC/R9 the decrease of GP activity at initial stages of tumor growth correlated with significant increase of GSH level in the tumor--by 250% (p < 0.01). It has been shown that in LLC/R9 tumors (unlike to LLC), GSH utilization is mostly provided by GST, its significantly higher activity has been detected in LLC/R9 tumors compared to LLC.
  
  
  CONCLUSIONS
  We have revealed a number of peculiarities of antioxidant system functioning in LLC and LLC/R9 tumors and have shown a relation between an activity of antioxidant system and some biological properties of studied tumor variants.
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: O N
authors.initials: ON
authors.lastname: Pyaskovskaya
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: L V
authors.initials: LV
authors.lastname: Sorokina
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: D L
authors.initials: DL
authors.lastname: Kolesnik
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: I V
authors.initials: IV
authors.lastname: Boichuk
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: O R
authors.initials: OR
authors.lastname: Melnikov
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: G I
authors.initials: GI
authors.lastname: Solyanik
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione