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 microM enhanced cell transformation initiated by a subthreshold dose (0.75 microM) 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 ([Ca(2+)]i) in BALB/3T3 cells. DTBHQ elevated [Ca(2+)]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 [Ca(2+)]i. Aberrant calcium signaling produced by DTBHQ might contribute to the enhancement of MCA-initiated transformation in BALB/3T3 cells.
Sakai
A
A
Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan. asakai.nihs.go.jp
Teshima
R
R
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006873:Hydroquinones / Q000494:pharmacology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C
D000975:Antioxidants; D002273:Carcinogens; D006873:Hydroquinones; C019359:2,5-di-tert-butylhydroquinone; D008748:Methylcholanthrene; C018855:2-tert-butylhydroquinone; D002118:Calcium