Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?
OBJECTIVE
Alimentary tract (AT) mucositis is a serious problem complicating cancer treatment, however, its pathobiology remains incompletely understood. Nuclear factor-kappaB (NF-kappaB) 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-kappaB, TNF, IL-1beta 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-kappaB 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.
Logan
Richard M
RM
Discipline of Oral Pathology, School of Dentistry, Faculty of Health Sciences, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia. richard.logan@adelaide.edu.au
Stringer
Andrea M
AM
Bowen
Joanne M
JM
Gibson
Rachel J
RJ
Sonis
Stephen T
ST
Keefe
Dorothy M K
DM
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000077146:Irinotecan; D007583:Jejunum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008727:Methotrexate / Q000009:adverse effects; D009061:Mouth Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D052016:Mucositis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000970:Antineoplastic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin; D008727:Methotrexate