Identification of genes differentially expressed in vascular smooth muscle cells following benzo[a]pyrene challenge: implications for chemical atherogenesis.

We have previously shown that serial passage of vascular smooth muscle cells (vSMCs) treated with a single low dose of benzo[a]pyrene (BaP) induces acquisition of highly proliferative (i.e. atherogenic) phenotypes. To define the molecular basis of this response, differential display polymerase chain reaction was used to identify early target genes in murine vSMCs challenged with 3 microM BaP for 8 hr. Of 170 differentially expressed cDNAs, 111 were re-amplified, and 64 examined for homology to known genes. Aac11 apoptosis inhibitor, aldose reductase, GalNAc transferase, TCP-1 chaperonin gene, and mouse mitochondrial gene, were downregulated in vSMCs treated with BaP. In contrast, enhanced expression of unique retrotransposon cDNAs were found in BaP-treated cells. This is the first report showing that BaP modulates the expression of these genes in mammalian cells. Of particular interest is the modulation of retrotransposon mRNAs which coupled to other genetic events, may play a significant role in the atherogenic response to this carcinogen.