2,5-Di-tert-butyl-1,4-hydroquinone enhances cell transformation accompanied by an increase in intracellular free calcium ion concentration

Two hydroquinones with similar structures, 2,5-di-tert-butyl-1,4-hydroquinone (DTBHQ) and 2-tert-butyl-1,4-hydroquinone (MTBHQ), are used as antioxidants in the environment. DTBHQ and MTBHQ were examined for their ability to induce cell transformation using BALB/3T3 cells. DTBHQ at concentrations of 2.5–15 μM enhanced cell transformation initiated by a subthreshold dose (0.75 μM) of 3-methylcholanthrene (MCA) in a two-stage cell transformation assay, which mimics a two-stage carcinogenicity test in experimental animals. Because DTBHQ is known to act as a calcium ion mobilizing agent in other cells, we examined the effects of DTBHQ on intracellular free calcium ion concentration ([Ca2+]i) in BALB/3T3 cells. DTBHQ elevated [Ca2+]i with a dose dependency similar to that of its enhancing effect on the MCA-initiated cell transformation. MTBHQ neither enhanced cell transformation nor induced increase of [Ca2+]i. Aberrant calcium signaling produced by DTBHQ might contribute to the enhancement of MCA-initiated transformation in BALB/3T3 cells.