Keith Huie

Mutagenicity and tumor initiating activity of methylated benzo [k] fluoranthenes

The mutagenic activities toward Salmonella typhimurium TA100 and tumor initiating activities on mouse skin of the polynuclear aromatic hydrocarbons benzo[k]fluoranthene (BkF),2-methylBkF,8-methylBkF,9-methyl-BkF and 7,12-dimethylBkF were compared. BkF and 2-methylBkF were the most mutagenic of the compounds tested and had comparable activity; they were more active than 7,12-dimethylBkF. 8-MethylBkF and 9-methylBkF were not mutagenic. BkF and the methylated BkFs had similar tumor initiating activities on mouse skin. The results suggest that 8,9-dihydro-8,9-epoxy-BkF might be involved in the metabolic activation of BkF to a mutagen, but do not indicate which metabolite may be involved in BkF tumorigenesis.

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.