Prolonged (90 min) incubation with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) causes no significant changes in the elemental composition of whole rabbit thymocytes (25 elements included). The only exception is the amount of magnesium, where a significant increase can be detected. However TPA preincubation elicits the redistribution of heavy metals (mainly Zn and to a much lesser extent Fe and Cu) from the nuclear and large granular (mitochondrial-lysosomal) fraction to the cytosol and microsomes. A significant translocation of calcium and phosphorus from the large granular fraction mainly to the nucleus can also be observed. The TPA-induced heavy metal depletion of the nucleus might play a role in the antiproliferative activity of TPA, the arrest of G1→S phase transition. On the other hand the increased amount of heavy metals in the cytosol might be linked to the TPA-induced block of intercellular communication and the desensitization of TPA-treated cells towards extracellular calcium which are well-known properties of neoplastic cells.
ASJC Scopus subject areas
- Cancer Research