Effect of 2-ITX on mRNA expression in the liver of male Wistar rats

2-Isopropylthioxanthone (2-ITX), a photoinitiator used in ink for printing of food packaging materials, has been detected in products like milk and fruit beverages. Previous in vitro research demonstrated 2-ITX to 1) exert agonistic effects on the aryl hydrocarbon receptor (AhR), 2) exert antagonistic effects on both the androgen (AR) and estrogen receptor (ER), and 3) to increase aromatase activity. To validate these findings in vivo, male rats were treated by gavage with 50, 150 or 500 mg 2-ITX/kg b.w. per day from postnatal day 23 to 53. For comparison, other groups were treated with 50 ng TCDD/kg b.w./day (AhR agonist), 30 mg bicalutamide/kg b.w./day (Casodex, AR antagonist) or 50 mg flutamide/kg b.w./day (AhR agonist and AR antagonist). 2-ITX, from the lowest dose onwards, decreased the weight of the ventral prostate, and from the middle dose onwards the weight of the seminal vesicles and coagulating gland. The highest dose of 2-ITX reduced the number of spermatozoa in the cauda of the epididymis. Similar effects, but more severe, were induced by flutamide and bicalutamide. Epididymal weight, caput sperm count and preputial separation were negatively affected by Casodex and flutamide but not by 2-ITX. The two highest doses of 2-ITX as well as TCDD increased liver weight. Whole genome mRNA expression profiling of the liver revealed similarity between the effects of 2-ITX and flutamide. In addition, many genes induced by TCDD were also induced by 2-ITX and flutamide. These results demonstrate 2-ITX to express AhR agonistic and AR antagonistic activities, both in vitro and in vivo