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Article Dans Une Revue Biotechnology Journal Année : 2010

In vivo bioassay to detect irinotecan-stabilized DNA/topoisomerase I complexes in rats

Stephan Barth
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Karlis Briviba
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Bernhard Watzl
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Nicole Jäger
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Résumé

Irinotecan is an anticancer agent stabilizing topoisomerase I/DNA complexes. No test system has been reported so far allowing to directly determining irinotecan-induced stabilization of topoisomerase I/DNA complexes in organs in vivo. We adapted a `in vivo complexes of enzyme to DNA` (ICE) bioassay to assess irinotecan activity in the stomach, duodenum, colon and liver of male Wistar rats after a single treatment with irinotecan (100 mg/kg body weight, intraperitoneally) compared to the control group receiving 0.9% sodium chloride intraperitoneally. In addition, the DNA strand breaking properties of irinotecan were measured in mucosal cells from the distal colon by single cell gel electrophoresis (comet-assay) to investigate the association of topoisomerase poisoning and DNA damage in vivo. A single dose of irinotecan significantly increased amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the irinotecan-treated group showed significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group. The ICE-bioassay and the comet assay represent two test systems for investigating the impact of topoisomerase I poisons on DNA-integrity in colon tissues of Wistar rats.

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Dates et versions

hal-00552333 , version 1 (06-01-2011)

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Stephan Barth, Karlis Briviba, Bernhard Watzl, Nicole Jäger, Doris Marko, et al.. In vivo bioassay to detect irinotecan-stabilized DNA/topoisomerase I complexes in rats. Biotechnology Journal, 2010, 5 (3), pp.321. ⟨10.1002/biot.200900174⟩. ⟨hal-00552333⟩

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