Irinotecan-induced gene expression changes in the rat intestine

The regional specificity and timing of gene activation following chemotherapy, and how this relates to subsequent mucositis development is currently unknown. The aim of the study was therefore to determine the early time course of gene expression changes along the gastrointestinal tract (GIT) of the DA rat following irinotecan treatment, so as to provide an insight into the genetic component of mucositis. We have found that changes in gene expression following irinotecan occur by 1 hour, and persist for at least 72 h after treatment. Overall changes in gene expression are similar along the GIT, however there is temporal variability between regions. Keywords: Time course and tissue comparison Thirty female DA rats were placed in groups (n = 6) and treated with 200 mg/kg i.p. of irinotecan. Animals were killed at 0, 1, 6, 24 and 72 h and samples of stomach, jejunum and colon collected. These times were chosen to represent very early responses to treatment, up to the time of peak damage and morphological changes. The 0 h group did not receive irinotecan and acted as experimental controls. RNA was extracted from whole tissue samples. RNA was pooled into 2 per group (n = 3) to allow for replication of experiment. Each sample was then hybridised to Affymetrix GeneChip Arrays (Rat 230 2.0).