Increase in hypoxic fraction of human colon tumor xenografts by preirradiation of tumor bed.
In these experiments, the normal tissue in the hip region of nude mice was irradiated with 15 Gy of x-rays. One day after irradiation, 1 X 10(7) clone A human adenocarcinoma cells were injected to produce solid xenograft tumors. The stromal damage produced by the x-rays yields inhibition of volumetric growth with the time needed to reach 500 mm3 about 2.2 times that seen in mice bearing tumors in nonirradiated tissue. At a volume of 500-600 mm3, tumors growing in either irradiated or nonirradiated stroma were either sham irradiated or irradiated with a single large dose of 30 Gy of x-rays. These mice were either breathing air or had been asphyxiated with nitrogen gas (10 min) immediately prior to exposure. Tumors were then excised, enzymatically disaggregated into single cells, and assayed in vitro for clonogenic cell survival. The hypoxic fractions were determined according to the parallel line bioassay technique. The hypoxic fraction in control (non-preirradiated mice) was 3.5%. However, the hypoxic fraction in tumors growing in preirradiated sites was 25.1%. Therefore, the growth of solid tumors in damaged normal tissue may be associated with an increased percentage of hypoxic cells, possibly produced by impairment of vascular supply.
Leith
J T
JT
Radiation Biology Laboratories, Brown University, Providence, RI.
D000818:Animals; D003110:Colonic Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous