Abstract
To examine potential variations in sensitivity of F344 rats from different breeders to carcinogens, groups of forty 6-week-old males from CLEA Inc., SLC Co., USA Charles River Co., and Japan Charles River Co. were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p., and 2 weeks later, they were given phenobarbital (PB) at a dose of 500 ppm. in the diet for 6 weeks and then sacrificed; all rats being subjected to two-thirds partial hepatectomy (PH) at week 3. Numbers and areas per cm2 of preneoplastic lesions, glutathione S-transferase placental form (GST-P) positive foci in the liver in this Ito test, were increased significantly in PB treated rats from all breeders compared with the corresponding control groups given DEN alone. The number of GST-P positive foci in animals from CLEA Japan, however, increased more than in rats from the other breeders. Assessment with Affymetrix Rat Genome 230 2.0 cDNA microarrays, revealed common changes in expression of genes between treated and control group rats from all sources. Hierarchical cluster analysis revealed the gene expression pattern to be quite similar for rats from USA Charles River Co. and Japan Charles River Co. Although the differences are very subtle, sensitivity of F344 rats to carcinogens may vary depending on breeders.
