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Genotoxicity of a carcinogenic metabolite of benzo[a]pyrene for cells of neuronal differentiation lineage

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

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Abstract:

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 develo- ping neural tissue. However, the effects of BPDE on cells with the ability to differentiate into the neuronal lineage may depend on the cell microenvironment.

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