DNA Adduct Formation by 2-Nitrofluoranthene in Salmonella typhimurium and Neonatal B6C3F₁ Mice

Abstract

In vivo studies of the metabolic activation of 2-nitrofluoranthene (2-NFA) were conducted by incubating Salmonella typhimurium TA98 suspension cultures with 2-NFA (10 or 20μM) for 4 hr. The DNA was isolated and the resulting DNA adducts were analyzed by HPLC and ³²P-postlabeling. In addition, neonatal mice were administered a total dose of 400 nmol 2-NFA in 35 μ1 dimethylsulfoxide (DMSO) by i.p. injection on 1, 8, and 15 days after birth with 1/7, 2/7, and 4/7, respectively, of the total dose. Livers were removed from the mice 24 hr, 48 hr, and 7 days after the last dose and the DNA isolated for ³²P-postlabeling adduct analysis. N−(Deoxyguanosin-8-yl)-2-aminofluoranthene and a second adduct were identified in the DNA from the Salmonella suspensions and one of these adducts was found in the neonatal mice. These results suggest that 2-NFA is metabolically activated to N−hydroxy-2-aminofluoranthene via nitroreduction and that the resulting DNA adduct is responsible for the mutagenic activities of 2-NFA.

Key Words:

• DNA adducts
• 2-nitrofluoranthene
• nitrated polycyclic aromatic hydrocarbons
• ³²P-postlabeling