title: Promotive effects of hyperthermia on the inhibition of DNA synthesis in ehrlich ascites tumor cells by eicosapentaenoic and docosahexaenoic acids.
abstract: OBJECTIVE
  To evaluate inhibitory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on DNA synthesis in combination with hyperthermia in vitro.
  
  
  METHODS
  A suspension of Ehrlich ascites tumor cells (EAT) was mixed with DHA or EPA in a glass tube, heated at 37 degrees C, 40 degrees C, or 42 degrees C for 1 h in a water bath, and cultured at 37 degrees C for 19 or 96 h. DNA synthesis was assayed by monitoring of the incorporation of [3H]-thymidine into the acid-insoluble fraction. DHA or EPA incorporated into EAT cells was extracted and measured by thin-layer chromatography and gas-liquid chromatography.
  
  
  RESULTS
  The inhibition of DNA synthesis by EPA or DHA increased markedly upon the treatment at 42 degrees C and 40 degrees C compared to that at 37 degrees C. At 37 degrees C, inhibitory action of EPA was more potent than that of DHA at low concentrations (at 50 microM -- DNA synthesis level: EPA, 63.1%; DHA, 87.9%), whereas inhibitory action of DHA was higher at 150 muM (16.7%, 4.4%, ibid.). The effect of DHA compared to EPA was more marked at 40 degrees C (29.0%, 19.2% at 100 microM) or 42 degrees C (19.7%, 10.6% at 100 microM). Evaluation of DNA synthesis rate in the cells treated for 1 h by EPA or DHA with the next culturing of EAT cells for 19 h resulted in the enhanced inhibitory activity of EPA even at concentrations as low as 50 microM at either 37 degrees C (0.5%, 11.3%) or 42 degrees C (0.6%, 4.5%), which in these conditions was higher than that of DHA. At the same time the rate of incorporation of EPA in EAT cells at 37 degrees C or 42 degrees C was lower than that of DHA.
  
  
  CONCLUSIONS
  Administration of DHA or EPA in vitro significantly inhibit DNA synthesis, and such effect is enhanced by combination of PUFAs with hyperthermia.
authors.affiliation: Osaka Butsuryo College, 3-33 Otorikita-cho, Sakai 593-8328, Japan. kageyama@butsuryo.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Kageyama
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: S I
authors.initials: SI
authors.lastname: Iwamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ueno
authors.forename: K
authors.initials: K
authors.lastname: Asagi
authors.forename: R
authors.initials: R
authors.lastname: Asada
authors.forename: N
authors.initials: N
authors.lastname: Miwa
mesh_terms: D000818:Animals; D001692:Biological Transport; D002286:Carcinoma, Ehrlich Tumor / Q000235:genetics*; D004261:DNA Replication / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology*; D006358:Hot Temperature; D014407:Tumor Cells, Cultured
chemical_list: D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid