Dataset Information

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

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.

SUBMITTER: Wadsworth BJ

PROVIDER: S-EPMC9130130 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Wadsworth Brennan J BJ Lee Che-Min CM Bennewith Kevin L KL

British journal of cancer 20220114 11

<h4>Background</h4>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.<h4>Methods</h4>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-modifyin ...[more]

PMID: 35031765

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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