Overexpression of human glutathione S-transferase pi protects NIH 3T3 cells against (+/-)anti BPDE cytotoxicity but not tumor formation.

Autor: Boucher DM; Department of Pathology and Pediatrics, Northwestern University Medical School, Chicago, IL 60614, USA., Iannaccone PM
Jazyk: angličtina
Zdroj: Pathobiology : journal of immunopathology, molecular and cellular biology [Pathobiology] 1995; Vol. 63 (4), pp. 197-203.
DOI: 10.1159/000163952
Abstrakt: In order to explore the protective function of human glutathione S-transferase pi (GST-pi) in vitro and in vivo, transfected NIH 3T3 clones were examined in cytotoxicity assays using the carcinogen (+/-)anti-benzo(a)pyrene 7,8-diol-9,10-epoxide (BPDE) or inoculated into nude mice and treated with the carcinogen benzo(a)pyrene (BP) to induce tumor formation. The human GST-pi cDNA under the control of the murine alpha 2(I)collagen promoter was transfected into NIH 3T3 cells and G418 resistant clones were analyzed by Southern, northern, western, and two-dimensional analysis. Clone A2 stably expressed human GST-pi and has 2.5-fold greater activity toward the substrate 1-chloro-2,4-dinitrobenzene and a 1.7-fold increase in LD50 for BPDE in vitro when compared to control-transfected clone G3. This increase in protection, however, did not prevent the formation of BP-induced tumors in vivo.
Databáze: MEDLINE