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Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?

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Abstract

Purpose

Alimentary tract (AT) mucositis is a serious problem complicating cancer treatment, however, its pathobiology remains incompletely understood. Nuclear factor-κB (NF-κB) and pro-inflammatory cytokines are considered to have important roles in its development. This has been previously demonstrated in different sites of the AT following administration of irinotecan in an animal model using the Dark Agouti rat. The aim of the present study was to determine whether the changes that occur in the AT are affected by the type of mucotoxic drug.

Methods

Female DA rats were given a single dose of either methotrexate (1.5 mg/kg intramuscularly) or 5-fluorouracil (150 mg/kg intraperitoneally). Rats were killed at 30, 60, 90 min, 2, 6, 12, 24, 48 and 72 h. Control rats received no treatment. Samples of oral mucosa, jejunum and colon were collected. Haematoxylin and eosin stained sections were examined with respect to histological evidence of damage and standard immunohistochemical techniques were used to demonstrate tissue expression of NF-κB, TNF, IL-1β and IL-6.

Results

Both MTX and 5-FU administration caused histological evidence of tissue damage in the AT as well as changes in tissue expression of NF-κB and specific pro-inflammatory cytokines. This study, however, demonstrated that there were differences in the timing of histological changes as well as the timing and intensity of pro-inflammatory cytokine tissue expression caused by the different drugs.

Conclusions

The results from this study suggest that there are differences in the mucositis pathobiology caused by different drugs. This may have important ramifications for the management of mucositis particularly with respect to the development of treatment regimens for mucositis. Further investigations are required to determine the exact pathways that lead to damage caused by the different drugs.

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Acknowledgments

This project was supported by a research grant awarded by the Royal Adelaide Hospital Research Committee and the Australian Dental Research Foundation Incorporated. Dr. Rachel Gibson was supported by a Cancer Council South Australia Research Fellowship; Dr. Joanne Bowen and Ms. Andrea Stringer by a Dawes Research Scholarship. Assistance with the statistical analysis for this study was provided by Mr. Thomas Sullivan from the Department of Public Health, The University of Adelaide. The authors also acknowledge Ms Marjorie Quinn, Oral Pathology, School of Dentistry, The University of Adelaide for her assistance in cutting sections.

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Authors and Affiliations

  1. Discipline of Oral Pathology, School of Dentistry, Faculty of Health Sciences, The University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia

    Richard M. Logan

  2. Division of Tissue Pathology, Institute of Medical and Veterinary Sciences, Adelaide, SA, 5000, Australia

    Richard M. Logan

  3. Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia

    Andrea M. Stringer, Joanne M. Bowen, Rachel J. Gibson & Dorothy M. K. Keefe

  4. Division of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia

    Andrea M. Stringer, Joanne M. Bowen, Rachel J. Gibson & Dorothy M. K. Keefe

  5. Brigham and Women’s Hospital, Boston, MA, USA

    Stephen T. Sonis

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  1. Richard M. Logan
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  2. Andrea M. Stringer
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  3. Joanne M. Bowen
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  4. Rachel J. Gibson
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  6. Dorothy M. K. Keefe
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Correspondence to Richard M. Logan.

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Logan, R.M., Stringer, A.M., Bowen, J.M. et al. Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?. Cancer Chemother Pharmacol 63, 239–251 (2009). https://doi.org/10.1007/s00280-008-0732-8

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  • DOI: https://doi.org/10.1007/s00280-008-0732-8

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