Transiently hypoxic tumour cell turnover and radiation sensitivity in human tumour xenografts.

Br J Cancer

Integrative Oncology, BC Cancer, Vancouver, BC, Canada.

Published: June 2022

AI Article Synopsis

  • Some cancer cells in tumors can have low oxygen levels, making them tough against radiation treatment, which is what we studied.
  • We looked at two types of tumor cells to see how long they stay low on oxygen and how they react to radiation and a special drug that increases oxygen.
  • We found that certain low-oxygen cells can survive for a while after radiation, but high doses of radiation can actually harm these cells due to blood flow problems.

Article Abstract

Background: Solid tumour perfusion can be unstable, creating transiently hypoxic cells that can contribute to radiation resistance. We investigated the in vivo lifetime of transiently hypoxic tumour cells and chronically hypoxic tumour cells during tumour growth and following irradiation.

Methods: Hypoxic cells in SiHa and WiDr human tumour xenografts were labelled using pimonidazole and EF5, and turnover was quantified as the loss of labelled cells over time. The perfusion-modifying drug pentoxifylline was used to reoxygenate transiently hypoxic cells prior to hypoxia marker administration or irradiation.

Results: Chronically hypoxic cells constantly turnover in SiHa and WiDr tumours, with half-lives ranging from 42-82 h and significant numbers surviving >96 h. Transiently hypoxic cells constitute 26% of the total hypoxic cells in WiDr tumours. These transiently hypoxic cells survive at least 24 h, but then rapidly turnover with a half-life of 34 h and are undetectable 72 h after labelling. Transiently hypoxic cells are radiation-resistant, although vascular dysfunction induced by 10 Gy of ionising radiation preferentially kills transiently hypoxic cells.

Conclusions: Transiently hypoxic tumour cells survive up to 72 h in WiDr tumours and are radiation-resistant, although transiently hypoxic cells are sensitive to vascular dysfunction induced by high doses of ionising radiation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130130PMC
http://dx.doi.org/10.1038/s41416-021-01691-5DOI Listing

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