title: Biphasic effect of a primary tumor on the growth of secondary tumor implants.
abstract: BACKGROUND
  The phenomenon of hormesis is characterized by a biphasic dose-response, exhibiting opposite effects in the low- and high-dose zones. In this study, we explored the possibility that the hormesis concept may describe the interactions between two tumors implanted in a single mouse, such that the resulting tumors are of different sizes.
  
  
  METHODS
  We used two murine tumors of spontaneous origin and undetectable immunogenicity growing in BALB/c mice. A measure of cell proliferation was obtained by immunostaining for Ki-67 protein and by using the [(3)H] thymidine uptake assay. For serum fractionation, we utilized dialysis and chromatography on Sephadex G-15.
  
  
  RESULTS
  The larger primary tumor induced inhibitory or stimulatory effects on the growth of the smaller secondary one, depending on the ratio between the mass of the larger tumor relative to that of the smaller one, with high ratios rendering inhibition and low ratios inducing stimulation of the secondary tumor.
  
  
  CONCLUSIONS
  Since metastases can be considered as natural secondary tumor implants in a tumor-bearing host and that they constitute the main problem in cancer pathology, the use of the concept of hormesis to describe those biphasic effects might have significant clinical implications. In effect, if the tumor-bearing host were placed in the inhibitory window, tumor extirpation could enhance the growth of distant metastases and, reciprocally, if placed in the stimulatory window, tumor extirpation would result not only in a reduction or elimination of primary tumor load but also in a slower growth or inhibition of metastases.
authors.affiliation: División Medicina Experimental (ILEX-CONICET), Academia Nacional de Medicina de Buenos Aires, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Bruzzo
authors.forename: Paula
authors.initials: P
authors.lastname: Chiarella
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Meiss
authors.forename: Raúl A
authors.initials: RA
authors.lastname: Ruggiero
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology*; D016609:Neoplasms, Second Primary / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse