Kim S, Thompson CM, Kopec AK, Harris MA, Zacharewski TR. 2011. Comparison of basal and CrVI-mediated solute carrier gene expression in rodent duodenal epithelium. Presented at the Society of Toxicology’s 50th Annual Meeting, March 6-10, Washington, D.C.
Hexavalent chromium (CrVI) is structurally similar to phosphate and sulfate ions and readily enters cells via anion transporters. Chronic administration of high doses of sodium dichromate dihydrate (SDD) leads to intestinal cancer in mice, but not in rats. To further evaluate species-specific differences in CrVI carcinogenicity, duodenal epithelia of female B6C3F1 mice and Fisher rats were examined after 7 days of continuous exposure to 0.3-520 mg/L SDD in drinking water. Whole genome 4x44K Agilent two-color oligonucleotide arrays identified basal expression of 289 unique solute carrier (SLC) transporter orthologs in control animals. SLC intensity values were normalized to the average signal intensity for all SLC orthologs. Overall, SLC expression levels were comparable between species with some notable exceptions. For example, there were species-specific differences (~86-20-fold) in the basal expression of SLC 35c1, 7a7, 6a20, 25a25, 5a11, 2a2, 25a4, 35d1, 25a25, and 35e2 in the mouse, while basal levels of SLC 25a4, 9a1, 30a3, 15a1, 44a4, 26a3, 4a4, 24a6, 35a4, and 39a8 were ~82-15-fold higher in the rat. Exposure to SDD differentially regulated 119 mouse and 48 rat SLC orthologs (|fold change|>1.5, P1(t)>0.999), of which 35 were commonly regulated in both species. The uptake of CrVI is believed to be mediated by Slc4a family, in agreement with high basal expression of Slc4a2 (3.5-fold) and Slc4a5 (2.1-fold) in the mouse, and Slc4a4 (13.4-fold) and Slc4a7 (21.3-fold) in the rat. SDD treatment did not affect expression of SLCs 4a2/5 in the mouse, but significantly repressed SLCs 4a4/7 in the rat at the highest doses. SLC4a1, the putative CrVI transporter, exhibited low basal expression and was not differentially regulated by SSD. The results suggest that CrVI exposure may alter SLC transporter expression. Differences in basal SLC expression and regulation could partially explain the observed carcinogenic phenotype differences between rats and mice.