Detection of the major DNA adducts of benzo[j]fluoranthene in mouse skin: Nonclassical dihydrodiol epoxides

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00031a018· OSTI ID:6442522

Weyand, E H ^[1]; Bryla, P; Wu, Yun; He, Z M; LaVoie, E J

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1. State Univ. of New Jersey, Piscataway (United States)

Studies have demonstrated that the metabolic activation of benzo[j]fluoranthene (B[j]F) to a genotoxic agent proceeds through the formation of either the trans-4,5-dihydrodiol (B[j]F-4,5-diol) or the trans-9,10-dihydrodiol (B[j]F-9,10-diol) metabolite of B[j]F. Using [sup 32]P-postlabeling analysis, the profiles of DNA adducts formed in vivo in mouse skin from B[j]F-4,5-diol and B[j]F-9,10-diol were obtained to establish the contribution of each of these dihydrodiols to the formation of B[j]F-DNA adducts in vivo. B[j]F, B[j]F-4,5-diol and B[j]F-9,10-diol were applied to the shaved backs of mice (100 [mu]g/mouse), and DNA adducts were isolated and separated using multidimensional TLC and reverse-phase HPLC. The greatest level of adducts observed was more than 2 orders of magnitude greater than that observed with B[j]F or B[j]F-9,10-diol. The major adducts detected from the application of B[j]F-4,5-diol to mouse skin in vivo had chromatographic properties similar to those of the major adducts detected with B[j]F. In contrast, the major DNA adducts detected with B[j]F-9,10-diol had chromatographic properties distinctly different than the adducts formed from either B[j]F or B[j]F-4,5-diol. DNA adducts formed from the syn and anti isomers of the 4,5-dihydrodiol 6,6a-epoxide and the 9,10-dihydrodiol 11,12-epoxide of B[j]F were also evaluated. Each dihydrodiol epoxide derivative was reacted with calf thymus DNA in vitro and applied to mouse skin in vivo. The DNA adducts formed in vitro were qualitatively similar to the adducts formed in vivo in mouse skin. The DNA adducts of each dihydrodiol epoxide derivative were also chromatographically similar to the major adducts isolated from mouse skin after application of the corresponding precursor dihydrodiol metabolite. The anti isomer formed considerably more DNA adducts than the syn isomer for each of the dihydrodiol epoxide derivatives evaluated. 34 refs., 6 figs., 2 tabs.

• OSTI ID: 6442522
• Journal Information: Chemical Research in Toxicology; (United States), Vol. 6:1; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA ADDUCTS
DETECTION
SYNTHESIS
EPOXIDES
MUTAGENESIS
BIOLOGICAL PATHWAYS
POLYCYCLIC AROMATIC HYDROCARBONS
CONDENSED AROMATICS
DNA
IN VITRO
IN VIVO
ISOMERS
METABOLIC ACTIVATION
METABOLISM
MICE
SKIN
ADDUCTS
ANIMALS
AROMATICS
BODY
HYDROCARBONS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
RODENTS
VERTEBRATES
550200* - Biochemistry
550300 - Cytology