This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sasaki, K. Articles by Kuroki, T. Search for Related Content PubMed PubMed Citation Articles by Sasaki, K. Articles by Kuroki, T.

Enhancement by 1,25-Dihydroxyvitamin D₃ of Chemically Induced Transformation of BALB 3T3 Cells without Induction of Ornithine Decarboxylase or Activation of Protein Kinase C¹

Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108 [K. S., K. C., H. H., N. K., T. K.]; and Department of Biochemistry, School of Dentistry, Showa University, Hatanodai, Shinagawa-ku, Tokyo 142 [E. A., T. S.], Japan

We reported previously that 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], a hormonally active form of vitamin D₃, markedly enhanced methylcholanthrene-induced transformation of BALB 3T3 A31-1-1 cells. When the cells were treated with methylcholanthrene (1 µg/ml) for 72 h and then with 1,25(OH)₂D₃ (5 ng/ml) for 2 wk, the transformation frequency was 1.95 ± 0.73 (SD) foci/dish in 8 independent experiments, which was about 20 times that in cultures treated with methylcholanthrene only. Even at a physiological concentration in plasma, i.e., 0.05 ng/ml, 1,25(OH)₂D₃ enhanced the transformation frequency significantly (P < 0.001). 1,25(OH)₂D₃ was not cytotoxic but slightly inhibited growth of the cells. Cells treated with 1,25(OH)₂D₃ were thin and became arranged in a meshwork with wide intercellular spaces. These morphological changes were reversible.

1,25(OH)₂D₃ induced DNA synthesis in quiescent BALB 3T3 cells dose and time dependently, but this effect was less than that of 12-O-tetradecanoylphorbol-13-acetate. Unlike 12-O-tetradecanoylphorbol-13-acetate, 1,25(OH)₂D₃ did not interfere with the binding of epidermal growth factor or phorbol dibutyrate. 1,25(OH)₂D₃ did not induce ornithine decarboxylase. Moreover, it did not activate protein kinase C in quiescent BALB 3T3 cells or this enzyme isolated from mouse brain.

BALB 3T3 cells and their transformants contain a specific cytosol receptor for 1,25(OH)₂D₃, but the binding sites of the transformants were fewer and had lower affinity than those of untransformed BALB 3T3 cells.

These effects of 1,25(OH)₂D₃ were specific, because other derivatives of vitamin D₃ induced the same effects only at 200 times or more higher concentrations.

¹ Supported in part by a grant for Cancer Research from the Ministry of Education, Science, and Culture of Japan.

² Present address: National Institute of Hygienic Sciences, kamiyoga 1-18-1, Setagaya-ku, Tokyo 158, Japan.

³ To whom requests for reprints should be addressed.

Received 10/11/84. Revised 7/24/85. Revised 10/24/85. Accepted 10/25/85.