| Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel. | |
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MedLine Citation:
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PMID: 7627965 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We reported previously (L. Milas et al., Cancer Res., 54: 3506-3510, 1994) that paclitaxel greatly enhances the response of a murine mammary carcinoma to subsequent irradiation and hypothesized that the enhanced radioresponse was mediated by tumor cell reoxygenation caused by treatment with paclitaxel. Because paclitaxel induced massive tumor cell destruction by apoptosis, it was reasoned that as apoptotic cells were removed from the tumor more hypoxic cells would have access to oxygen, be reoxygenated, and, thus, become more sensitive to radiation. The present study tested this hypothesis by assessing the effect of 60 or 40 mg/kg paclitaxel on radioresponse of an 8-mm MCA-4 tumor irradiated under air-breathing or hypoxic conditions 9, 24, 48, or 72 h after paclitaxel administration. If the hypothesis was correct, paclitaxel would enhance tumor radioresponse more under air breathing than under hypoxic conditions, and the enhancement would increase as the time between paclitaxel administration and tumor irradiation increased within a few days after paclitaxel treatment but only when radiation was given under air-breathing conditions. The effect of the treatments was determined by tumor growth delay and the radiation dose required to control 50% of the tumors (TCD50). Paclitaxel greatly enhanced tumor radioresponse under air-breathing (and not hypoxic) conditions, increasing tumor growth delay, and reducing TCD50. These effects increased as the time interval between paclitaxel administration and tumor irradiation increased within the observation period of 72 h after paclitaxel treatment. The enhancement factors for tumor growth delay ranged from 1.19 at 9 h to 1.86 at 48 h and for TCD50, from 1.16 at 9 h to 1.47 at 72 h after paclitaxel. Direct measurements of tumor pO2 showed a median value in untreated tumors of 6.2 mmHg, which increased to 10.5 mmHg at 24 h and to 31.2 mmHg at 48 h after paclitaxel administration. Overall, these results show that paclitaxel is a potent enhancer of tumor radioresponse and that its effect is mediated by reoxygenation of hypoxic tumor cells. |
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Authors:
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L Milas; N R Hunter; K A Mason; C G Milross; Y Saito; L J Peters |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 55 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1995 Aug |
Date Detail:
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Created Date: 1995-09-07 Completed Date: 1995-09-07 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 3564-8 Citation Subset: IM |
Affiliation:
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Department of Experimental Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / metabolism Drug Administration Schedule Male Mammary Neoplasms, Experimental / drug therapy, radiotherapy, therapy* Mice Mice, Inbred C3H Oxygen / metabolism* Paclitaxel / pharmacology* Radiation-Sensitizing Agents / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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CA-06294/CA/NCI NIH HHS; CA-16672/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Radiation-Sensitizing Agents; 33069-62-4/Paclitaxel; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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