Biopolymers and Cell. 2012; 28(4): 298-301

 

GENOTOXICITY OF A CARCINOGENIC METABOLITE OF BENZO[A]PYRENE FOR CELLS OF NEURONAL DIFFERENTIATION LINEAGE

 

Endutkin A. V., 1Sidorenko V. S., Zharkov D. O.


Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
8, Akademika Lavrentieva Ave., Novosibirsk, Russian Federation, 630090

1Department of Pharmacological Sciences, Stony Brook University Stony Brook
NY 11794-8651, USA

Aim. Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) is the major metabolite of an environmental carcinogen, polycyclic aromatic hydrocarbon benzo[a]pyrene. The effects BPDE could have on neuronal cells progenitors are mostly uncharacterized. Methods. We have studied survival and morphology of cultured PC12 cells and mouse embryonic hippocampal neurons in the presence of BPDE. We have also used post-labeling to compare accumulation of BPDE adducts in cultured PC12 cells and fibroblasts. Results. The survival of cells and the level of adducts depended on the type of extracellular matrix to which the cells were attached. At tolerated BPDE doses, the adducts formed by this metabolite were efficiently repaired. In PC12 cells, BPDE toxicity and the level of adducts was generally lower than in fibroblasts. Conclusions. Overall, BPDE may be detrimental for developing neural tissue. However, the effects of BPDE on cells with the ability to differentiate into the neuronal lineage may depend on the cell microenvironment.

 


Keywords: DNA damage, DNA repair, genotoxicity, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, neuronal lineage