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-hydroquino ne (DTBHQ) and 2-tert-butyl-1,4-hydroquinone (MTBHQ), are used as antioxida nts 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 muM enhanced cell transformation initiated by a subthreshold dose ( 0.75 muM) of 3-methylcholanthrene (MCA) in a two-stage cell transformation assay, which mimics a two-stage carcinogenicity test in experimental animal s. 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-initia ted cell transformation. MTBHQ neither enhanced cell transformation nor ind uced increase of [Ca2+](i). Aberrant calcium signaling produced by DTBHQ mi ght contribute to the enhancement of MCA-initiated transformation in BALB/3 T3 cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.