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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Cytotoxicity, cellular transformation and DNA adducts in normal human diploid fibroblasts exposed to 1-nitrosopyrene, a reduced derivative of the environmental contaminant, 1-nitropyrene.

Treatment of normal human diploid fibroblasts with 0.3-22 microM 1-nitrosopyrene resulted in a dose-dependent decrease in relative cloning efficiency and an increase in anchorage-independent growth in soft agar. When compared to previous experiments, 1-nitrosopyrene was 10- to 20-fold more cytotoxic and 5- to 10-fold more potent at inducing morphological transformation than 1-nitropyrene. Incubation of the fibroblasts with 8 microM 1-nitropyrene in the presence of xanthine oxidase, a mammalian nitroreductase, resulted in the formation of one major DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene, at a level of 1.1 adducts per 10(6) nucleotides. Fibroblasts treated with 1-nitrosopyrene formed the same DNA adduct; however, only a 0.3 microM concentration was required to give 0.7 adducts per 10(6) nucleotides in the fibroblast DNA. These data indicate that a limiting step in the cellular toxicity and transformation of normal human diploid fibroblasts by 1-nitropyrene is the initial reduction to 1-nitrosopyrene.[1]

References

  1. Cytotoxicity, cellular transformation and DNA adducts in normal human diploid fibroblasts exposed to 1-nitrosopyrene, a reduced derivative of the environmental contaminant, 1-nitropyrene. Beland, F.A., Ribovich, M., Howard, P.C., Heflich, R.H., Kurian, P., Milo, G.E. Carcinogenesis (1986) [Pubmed]
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