title: Connaught and Russian strains showed the highest direct antitumor effects of different Bacillus Calmette-Guérin substrains.
abstract: OBJECTIVE
  Evolutionarily early and late bacillus Calmette-Guérin substrains are genetically distinct, showing different antigenic determinants. While it was suggested that this may influence the immunostimulatory effects of bacillus Calmette-Guérin as a vaccine in the context of tuberculosis, to our knowledge the impact of these genetic differences on the antitumor activity of bacillus Calmette-Guérin remains unknown. We compared the direct antitumor capacity and the ability to trigger cytokine production of 8 evolutionarily early and late BCG substrains in urothelial bladder cancer cell lines.
  
  
  METHODS
  The T24, J82 and RT4 bladder tumor cell lines were cultured with different doses of 3 evolutionarily early bacillus Calmette-Guérin substrains (Japan, Moreau and Russian) and 5 evolutionarily late strains (Connaught, Danish, Glaxo, Phipps and Tice). The inhibition of cell proliferation at different time points and the production of interleukin-6 and 8 in cell culture supernatants were measured.
  
  
  RESULTS
  For T24 and J82 cells Russian and Connaught induced the highest inhibition of cell proliferation and cytokine production, triggering values up to threefold higher than the other bacillus Calmette-Guérin strains. In contrast, Glaxo and Phipps (for T24 cells) and Glaxo and Tice (for J82 cells) were the least efficacious. For RT4 all bacillus Calmette-Guérin strains inhibited cell proliferation to a similar extent and induced low levels of only interleukin-8 except the Danish and Glaxo strains, which were less efficacious.
  
  
  CONCLUSIONS
  Russian and Connaught, which are evolutionarily early and late substrains, respectively, are the most efficacious bacillus Calmette-Guérin strains for inhibiting cell proliferation and inducing cytokine production. Glaxo is the least efficacious strain.
authors.affiliation: Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Secanella-Fandos
authors.forename: Marina
authors.initials: M
authors.lastname: Luquin
authors.forename: Esther
authors.initials: E
authors.lastname: Julián
mesh_terms: D001500:BCG Vaccine / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D006801:Humans; D009163:Mycobacterium bovis / Q000145:classification* / Q000235:genetics*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D001500:BCG Vaccine