Modulatory effects of polycyclic aromatic hydrocarbons on the mutagenicity of 1-nitropyrene: A structure-activity relationship study

Shur Hueih Cherng, Shaw Tao Lin, Huei Lee

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Benzo[a]pyrene (B[a]P) is able to inhibit the mutagenicity of 1-nitropyrene (1-NP) through the reduction of nitroreductase activity and formation of adducts with DNA. The relationship between the chemical structure of 9 polycyclic aromatic hydrocarbons (PAHs) and antagonistic effects on the 1-NP-induced mutation were evaluated by the binary mixtures of 1-NP and PAHs with Salmonella typhimurium TA98 in the absence of S9 mix. Remarkably different antagonistic effects of 9 PAHs on the mutagenicity of 1-NP were observed. Among the tested PAHs, coronene demonstrates the most antagonistic potential followed by benzo[g,h,i]perylene (B[g,h,i]P), benzo[e]pyrene (B[e]P), dibenzo[a,h]pyrene (DB[a,h]P), benzo[a]pyrene (B[a]P) and pyrene. Naphthalene, anthracene, and chrysene had only minor inhibitory activity on the 1-NP mutagenicity. The modifying effects of PAHs on the nitroreductase activity of TA98 strains in the presence of 1-NP were further examined from the production of 1-AP. The statistical analytical data showed that the inhibitory effect of PAHs on the mutagenicity of 1-NP significantly correlated with their effects on the nitroreductase activity (r = -0.69, p <0.05). In addition, the formation of 1-NP-DNA adducts of the binary mixtures of 1-NP and PAH was determined by the 32P-postlabeled method. The results indicated that the modulatory effects of PAHs on the formation of 1-NP-DNA adducts were correlated well with their antagonistic activity (r = -0.91, P <0.01). From the above results, the relationships between the chemical structure of PAHs and the antagonistic effects of the 1-NP mutagenicity were revealed by the surface area and electronic parameters of PAHs. The planar molecular area of PAHs was more convincingly correlated with the antagonistic effect on the mutagenicity of 1-NP (r = 0.81, p <0.01) than that with the difference in energy, ΔE, between E(HOMO) and E(LUMO) (r = 0.69, p <0.05). According to the above, two possible mechanisms are involved in the interactive effect of the binary mixtures: (1) a higher binding affinity with nitroreductase for PAHs having a large planar surface area; and (2) a high energy of interaction between 1-NP and PAHs with a low ΔE might decrease the nitroreductive capability.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalMutation Research - Genetic Toxicology
Issue number4
Publication statusPublished - 1996
Externally publishedYes



  • 1-Nitropyrene
  • DNA adduct
  • Nitroreductase
  • Polycyclic aromatic hydrocarbon

ASJC Scopus subject areas

  • Toxicology
  • Genetics

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