Effects of fluorine substitution on the DNA binding and tumorigenicity of benzo[b]fluoranthene in mouse epidermis.
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-post-labelling 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.
Weyand
E H
EH
American Health Foundation, Naylor Dana Institute for Disease Prevention, Valhalla, NY 10595.
Amin
S
S
Huie
K
K
Boger
E
E
Neuber
E
E
Hecht
S S
SS
LaVoie
E J
EJ
D000818:Animals; D004247:DNA / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D015394:Molecular Structure; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013329:Structure-Activity Relationship
D005449:Fluorenes; D004247:DNA; C006703:benzo(b)fluoranthene