Carcinogenesis, Vol. 23, No. 1, 47-53,
January 2002
© 2002 Oxford University Press
CANCER BIOLOGY |
Effect of soluble and particulate nickel compounds on the formation and repair of stable benzo[a]pyrene DNA adducts in human lung cells
1 Institut für Lebensmittelchemie und Toxikologie, Universität Karlsruhe, D-76128 Karlsruhe and
2 Biochemisches Institut für Umweltcarcinogene, Prof Dr G.Grimmer-Stiftung, D-22927 Grosshansdorf, Germany
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.
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