Journal
TOXICOLOGY IN VITRO
Volume 25, Issue 5, Pages 1007-1017Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2011.03.018
Keywords
Benzo(a)pyrene; BPDE-DNA adducts; p53 Phosphorylation; Cell viability; TP53 mutation
Categories
Funding
- Finnish Graduate School in Toxicology
Ask authors/readers for more resources
To know whether the molecular responses to chemical carcinogens reflect only cell line specific molecular responses, or whether they can be regarded as characteristic of breast tissue, we have characterized four human breast cancer cell lines (MDA-MB-231, MDA-MB-468, T47-D, ZR-75-1). The activation of benzo(a)pyrene (BP), a model compound of polycyclic aromatic hydrocarbons, to its genotoxic BP-diolepoxide (BPDE) and p53 response and cell viability after BP exposure, and the p53 status in these cell lines were analyzed. Both TP53 (exons 5-8) mutations and total and phospho-p53 were analyzed. Three of the four cell lines clearly activated BP to BPDE-DNA adducts (MDA-MB-468, T47-D, ZR-75-1) and three had a mutation in the TP53 gene (MDA-MB-231, MDA-MB-468, T47-D). After BP-treatment the strongest p53 protein induction and phosphorylation at serine 392 was found in ZR-75-1 cells with a wt TP53 gene. Viability decreased dramatically only in ZR-75-1 and MDA-MB-468 cells although the relative cell number was reduced in all the cell lines suggesting that BP affects cell proliferation. In conclusion, a TP53 mutation does not necessarily lead to a loss of p53 protein response. This study stresses the importance of characterization of all human cancer cell lines for the intended targets of study. (C) 2011 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available