Journal Article

Effect of soluble and particulate nickel compounds on the formation and repair of stable benzo[<i>a</i>]pyrene DNA adducts in human lung cells

Tanja Schwerdtle, Albrecht Seidel and Andrea Hartwig

in Carcinogenesis

Volume 23, issue 1, pages 47-53
Published in print January 2002 | ISSN: 0143-3334
Published online January 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.1.47
Effect of soluble and particulate nickel compounds on the formation and repair of stable benzo[a]pyrene DNA adducts in human lung cells

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Nickel compounds are well-known human carcinogens, but the underlying mechanisms are still not fully understood. Even though only weakly mutagenic, nickel chloride has been shown previously to impair the repair of UV-induced DNA damage as well as oxidative DNA damage. However, the carcinogenic potential depends largely on solubility, with poorly water-soluble nickel subsulfide and nickel oxide being strong carcinogens. Within the present study we investigated the effects of particulate black NiO and soluble NiCl2 on the induction and removal of stable DNA adducts formed by benzo[a]pyrene (B[a]P) measured by a highly sensitive high performance liquid chromatography (HPLC)/fluorescence assay. With respect to adduct formation, NiO but not NiCl2 reduced the generation of DNA lesions by ∼30%. Regarding their repair, in the absence of nickel compounds, most lesions were removed within 24 h; nevertheless, between 20 and 35% of induced adducts remained even 48 h after treatment. NiCl2 and NiO reduced the removal of adducts in a dose-dependent manner. Thus, 100 μM NiCl2 led to ∼80% residual repair capacity; after 500 μM the repair was reduced to ∼36%. Also, even at the completely non-cytotoxic concentration of 0.5 μg/cm2 black NiO, lesion removal was reduced to ∼35% of control and to 15% at 2.0 μg/cm2. Furthermore, both nickel compounds increased the benzo[a]pyrene-7,8-diol 9,10-epoxide (BPDE)-induced cytotoxicity. Taken together, our results indicate that the nucleotide excision repair pathway is affected in general by water-soluble and particulate nickel compounds and provide further evidence that DNA repair inhibition may be one predominant mechanism in nickel-induced carcinogenicity.

Keywords: B[a]P, benzo[a]pyrene; BPDE, benzo[a]pyrene-7,8-diol 9,10-epoxide; DMEM, Dulbecco's modified eagle medium; GG-NER, global genome nucleotide excision repair; HPLC, high performance liquid chromatography; MEM, minimal essential medium; NER, nucleotide excision repair; PAH, polycyclic aromatic hydrocarbons; TC-NER, transcription-coupled nucleotide excision repair; tetrol I-1, r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene; THF, tetrahydrofuran

Journal Article.  5608 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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