title: Genotoxic effects of benzo[a]pyrene and dibenzo[a,l]pyrene in a human lung cell line.
abstract: Several studies have shown that polycyclic aromatic hydrocarbons (PAHs) produce genotoxic effects in assays performed in vivo and in vitro. This study was undertaken to investigate the ability of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) to induce DNA damage in a human lung fibroblast cell line (MRC-5), using sister-chromatid exchanges test (SCEs), the comet assay, and evaluating point mutations in codon 12 of the K-ras protooncogene by polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCPs) and restriction fragment length polymorphisms (RFLP)-enriched PCR methods. Sister-chromatid exchanges frequencies were significantly increased in cells exposed to benzo[a]pyrene and dibenzo[a,l]pyrene in relation to controls (p < .001). Using the standard alkaline comet assay, significant differences between groups were found for the variable comet moment (CM) when cells were exposed to BP (p < .001) and DBP (p < .001). Nevertheless, PCR-SSCP and RFLP-enriched PCR methods did not show any association between treatments with BP and DBP and K-ras point mutations. The data presented in this study indicated that BP and DBP induced both DNA strand breaks and sister-chromatid exchanges but not significant point mutations at codon 12 of K-ras gene in the MRC-5 cell line.
authors.affiliation: Centro de Investigaciones en Genética Básica y Aplicada (CIGEBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Silvana Andrea
authors.initials: SA
authors.lastname: Mourón
authors.forename: Claudia Alejandra
authors.initials: CA
authors.lastname: Grillo
authors.forename: Fernando Noel
authors.initials: FN
authors.lastname: Dulout
authors.forename: Carlos Daniel
authors.initials: CD
authors.lastname: Golijow
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D001580:Benzopyrenes / Q000633:toxicity*; D002460:Cell Line; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation / Q000187:drug effects; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D012854:Sister Chromatid Exchange / Q000187:drug effects
chemical_list: D001580:Benzopyrenes; D009153:Mutagens; D001564:Benzo(a)pyrene; D004247:DNA; C041517:dibenzo(a,l)pyrene