This study examined the effect of exogenous @entity3014 ( @entity3015 ), an important constituent of cigarette smoke, on cultured @entity291 retinal pigment epithelial (RPE) cells. Evidence is presented for its metabolic conversion into @entity4624 ( @entity12847 ) and the consequent formation of potentially cytotoxic nucleobase adducts in DNA. Cultured RPE cells were treated with @entity3015 at concentrations in the range of 0-100 microM. The presence of @entity3015 was found to cause inhibition of cell growth and replication. @entity3015 induced the expression of a phase I drug metabolizing enzyme which was identified as @entity69235 ( @entity69235 ) by RT-PCR and by Western blotting. Coincident with the increased expression of @entity69235 , covalent adducts between the mutagenic metabolite @entity12847 and DNA could be detected within RPE cells by immunocytochemical staining. Additional support for their formation was afforded by nuclease P1 enhanced @entity7263 -postlabelling assays on cellular DNA. Single-cell gel electrophoresis (comet) assays showed that exposure of RPE cells to @entity3015 rendered them markedly more susceptible to DNA damage induced by broad band UVB or blue light laser irradiation. In the case of UVB, this is consistent with the photosensitization of DNA cleavage by nucleobase adducts of @entity12847 . Collectively, these findings imply that @entity3015 has a significant impact on RPE cell pathophysiology and suggest mechanisms whereby exposure to cigarette smoke might cause @entity989 and cell death, thus possibly contributing to @entity179 .

Retinal pigment epithelial cell DNA is damaged by exposure to XXXX , a constituent of cigarette smoke.

@entity7263 :: ('CHEBI:37972', 'Chemical') :: ['(32)P'] @entity3014 :: ('MESH:D001564', 'Chemical') :: ['benzo[ a ]pyrene'] @entity3015 :: ('CHEBI:29022', 'Chemical') :: ['BaP'] @entity179 :: ('MESH:D019636', 'Disease') :: ['degenerative disorders of the retina'] @entity12847 :: ('MESH:D015123', 'Chemical') :: ['BPDE'] @entity989 :: ('MESH:D012164', 'Disease') :: ['RPE dysfunction'] @entity4624 :: ('CHEBI:30614', 'Chemical') :: ['benzo[ a ]pyrene diol epoxide'] @entity69235 :: ('282870(Tax:9913)', 'Gene') :: ['CYP 1A1', 'cytochrome P450 1A1'] @entity291 :: ('9913', 'Species') :: ['bovine']
@entity3014 :: (MESH:D001564,Chemical) :: ['benzo[a]pyrene']
