Irinotecan-induced mucositis is associated with changes in intestinal mucins.
OBJECTIVE
Mucositis is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy and radiotherapy. Irinotecan is used to treat a variety of solid tumours, through the inhibition of DNA topoisomerase I and is linked with severe mucositis and diarrhoea. Mucus production appears to be increased, which may contribute to the development of diarrhoea.


METHODS
Dark agouti rats were treated with irinotecan, and tissues collected at several time points up to 72 h. Goblet cells and mucin secretion were investigated, as well as mucin expression (Muc2 and Muc4) and kruppel-like factor (Klf) 4 using immunohistochemistry in the gastrointestinal tract. Both goblet cells and cells positive for Muc expression were counted, and analysed statistically using the Mann-Whitney U test with Bonferroni correction.


RESULTS
Goblet cells decreased significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon.


CONCLUSIONS
Irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea.
Stringer
Andrea M
AM
Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, Australia. andrea.stringer@imvs.sa.gov.au
Gibson
Rachel J
RJ
Logan
Richard M
RM
Bowen
Joanne M
JM
Yeoh
Ann S J
AS
Laurence
Jessica
J
Keefe
Dorothy M K
DM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D000077146:Irinotecan; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000187:drug effects / Q000378:metabolism; D055262:Mucin-2 / Q000187:drug effects / Q000235:genetics; D055264:Mucin-4 / Q000187:drug effects / Q000235:genetics; D009077:Mucins / Q000187:drug effects* / Q000378:metabolism; D052016:Mucositis / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D018709:Statistics, Nonparametric; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D055262:Mucin-2; D055264:Mucin-4; D009077:Mucins; D000077146:Irinotecan; D002166:Camptothecin