Induction of p53 protein expression by sodium arsenite.
Arsenic is carcinogen for humans and has been shown to act as an enhancer in initiated animal models. In a previous work we found impairment of lymphocyte proliferation in arsenic-exposed individuals and in vitro we obtained dose-related inhibition of mitotic response and lymphocyte proliferation. Intrigued by these effects and based on the role of p53 on cell proliferation, we tested different concentrations of sodium arsenite for their ability to induce the expression of tumor suppressor gene p53 in different cell lines (HeLa, C-33A. Jurkat) and a lymphoblast cell line transformed with Epstein-Barr virus (LCL-EBV). We also evaluated changes in their viability after 24 h arsenic treatment; C-33A cells showed the higher sensitivity to arsenic treatment while HeLa, Jurkat and LCL-EBV cells showed similar cytotoxicity curves. Immunoblots showed an increased expression of p53 gene with 1 microM sodium arsenite in Jurkat cells and 10 microM sodium arsenite in HeLa and LCL-EBV cells. In addition, we transfected Jurkat cells and human lymphocytes with wild-type and mutated p53 genes; lymphocytes and Jurkat cells that received the mutated p53 showed increased sensitivity to arsenic cytotoxicity. Data obtained indicate that arsenic induces p53 expression and that cells with a functional p53 contend better with damage induced by this metalloid.
Salazar
A M
AM
Departamento de Genética y Toxicología Ambiental, U.N.A.M., México, Mexico.
Ostrosky-Wegman
P
P
Menéndez
D
D
Miranda
E
E
García-Carrancá
A
A
Rojas
E
E
D018053:Arsenites / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002277:Carcinoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D016158:Genes, p53; D006367:HeLa Cells / Q000187:drug effects; D004854:Herpesvirus 4, Human; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D017670:Sodium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D018053:Arsenites; D002273:Carcinogens; D017670:Sodium Compounds; D016159:Tumor Suppressor Protein p53; C017947:sodium arsenite