Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8- Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest

We show here that arsenite (As3) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G2/M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the ques-tion as to whether As3 is selectively inhibiting TCDD induction of CYP1A1 independent of cell cycle control. As3 stimulated a concentration-dependent increase in G2/M phase arrest that was detected at 12.5 M As3. However, cotreatment of HepG2 cells with TCDD and concentrations of As3 as low as 0.5 M stimulated a pronounced decrease in the induction of CYP1A1-dependent ethoxyresorufin-O-deethylase activity and protein, indicating that the inhibition of CYP1A1 induction by As3 was considerably more sensitive than As3-initiated cel