- Tomoki Kimura (Department of Life Science, Faculty of Science and Engineering, Setsunan University / firstname.lastname@example.org)
1) Department of Life Science, Faculty of Science and Engineering, Setsunan University , 2) Laboratory of Environmental and Molecular Toxicology, Department of Health Science, Yokohama University of Pharmacy , 3) Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University
Cadmium is an environmental pollutant. Metallothioneins are cysteine-rich, low-molecular-weight proteins that are induced by cadmium, which they chelate for detoxification. In humans, the functional metallothionein isoforms are MT1A, 1B, 1E, 1F, 1G, 1H, 1M, 1X, 2A, 3, and 4. It has been reported that overexpression of MT1G inhibits all-trans-retinoic acid (ATRA)–induced hematopoietic differentiation. Here, we found that cadmium inhibited ATRA-induced nitroblue tetrazolium reduction activity, a marker of hematopoietic differentiation, in human acute myelocytic leukemia HL-60 cells. Reverse transcription – quantitative polymerase chain reaction analysis of HL-60 cells revealed the expression of the metallothionein isoforms MT1G, MT1X, and MT2A and showed that MT1G expression increased significantly after cadmium treatment. ATRA treatment significantly attenuated this cadmium-induced increase in MT1G expression; however, MT1G expression remained significantly higher than that in untreated cells. No significant changes in MT1X and MT2A expression were observed. We also found that the cadmium-induced increase in MT1G expression was independent of CpG demethylation. ATRA is a standard chemotherapy treatment for acute promyelocytic leukemia; our findings suggest that cadmium may inhibit the effect of this chemotherapy.