TY - JOUR
T1 - Effects of fluorine substitution on the DNA binding and tumorigenicity of benzo[b]fluoranthene in mouse epidermis
AU - Weyand, Eric H.
AU - Amin, Shantu
AU - Huie, Keith
AU - Boger, Eliahu
AU - Neuber, Evelyn
AU - Hecht, Stephen S.
AU - LaVoie, Edmond J.
N1 - Funding Information:
This study was supported by Grant No. CA-44377 from the National Cancer Institute and Grant No. ES-02030 from the National Institute of Environmental Health and Sciences.
PY - 1989
Y1 - 1989
N2 - The effects of fluorine substitution on benzo[b]fluoranthene (B[b]F) DNA adduct formation and tumorigenicity in mouse epidermis were investigated. Fluoro derivatives studied included 1-, 6-, 7-, 8-, 9- and 11-fluoroB[b]F as well as 1,9- and 6,9-difluoroB[b]F. Each compound was applied topically to mice and hydrocarbon/DNA adduct formation was assessed using the 32P-postlabelling technique. All of the fluorinated compounds bound to DNA to a lesser extent than B[b]F. Among the fluorinated compounds, the greatest binding was observed for 8-fluoroB[b]F. Lowest levels of hydrocarbon/DNA adduct formation from the fluoro derivatives were observed for 1-, 7-, 11- and 6,9-difluoroB[b]F. The tumor-initiating activities on mouse skin of 7-, 9- and 11-fluoroB[b]F were determined. All three compounds were significantly less tumorigenic than B[b]F. The results of this study are discussed with respect to possible mechanisms of metabolic activation of B[b]F.
AB - The effects of fluorine substitution on benzo[b]fluoranthene (B[b]F) DNA adduct formation and tumorigenicity in mouse epidermis were investigated. Fluoro derivatives studied included 1-, 6-, 7-, 8-, 9- and 11-fluoroB[b]F as well as 1,9- and 6,9-difluoroB[b]F. Each compound was applied topically to mice and hydrocarbon/DNA adduct formation was assessed using the 32P-postlabelling technique. All of the fluorinated compounds bound to DNA to a lesser extent than B[b]F. Among the fluorinated compounds, the greatest binding was observed for 8-fluoroB[b]F. Lowest levels of hydrocarbon/DNA adduct formation from the fluoro derivatives were observed for 1-, 7-, 11- and 6,9-difluoroB[b]F. The tumor-initiating activities on mouse skin of 7-, 9- and 11-fluoroB[b]F were determined. All three compounds were significantly less tumorigenic than B[b]F. The results of this study are discussed with respect to possible mechanisms of metabolic activation of B[b]F.
KW - Fluorine
KW - P-postlabelling
KW - Polycyclic aromatic hydrocarbons
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U2 - 10.1016/0009-2797(89)90041-0
DO - 10.1016/0009-2797(89)90041-0
M3 - Article
C2 - 2598303
AN - SCOPUS:0024426917
SN - 0009-2797
VL - 71
SP - 279
EP - 290
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 2-3
ER -