title: pO₂ fluctuation pattern and cycling hypoxia in human cervical carcinoma and melanoma xenografts.
abstract: OBJECTIVE
  Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO(2)) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO(2) fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels.
  
  
  METHODS
  Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO(2) was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia.
  
  
  RESULTS
  The proportion of tumor regions showing pO(2) fluctuations, the pO(2) fluctuation frequency in these regions, and the relative amplitude of the pO(2) fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts.
  
  
  CONCLUSIONS
  Temporal heterogeneity in blood flow and tissue pO(2) in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO(2) and, thus, protect tumor tissue from cycling hypoxia.
authors.affiliation: Radiation Biology and Tumor Physiology Group, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Christine
authors.initials: C
authors.lastname: Ellingsen
authors.forename: Kirsti Marie
authors.initials: KM
authors.lastname: Ovrebø
authors.forename: Kanthi
authors.initials: K
authors.lastname: Galappathi
authors.forename: Berit
authors.initials: B
authors.lastname: Mathiesen
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000032:analysis; D003238:Connective Tissue / Q000098:blood supply*; D005260:Female; D006801:Humans; D008545:Melanoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009593:Nitroimidazoles / Q000032:analysis; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010313:Partial Pressure; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology
chemical_list: D004396:Coloring Agents; D009593:Nitroimidazoles; C033815:pimonidazole; D010100:Oxygen