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Comparative mutagenicity of nitrofluoranthenes in salmonella typhimurium TA98, TA98NR, and TA98/1,8DNP 6
Author(s) -
Shane B. S.,
Squadrito G. L.,
Church D. F.,
Pryor W. A.,
MacPhee D. G.
Publication year - 1991
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850170210
Subject(s) - nitration , fluoranthene , chemistry , nitroreductase , electrophile , mutagen , nitro , potency , steric effects , nitro compound , electrophilic substitution , stereochemistry , medicinal chemistry , biochemistry , organic chemistry , carcinogen , pyrene , alkyl , in vitro , enzyme , catalysis
The nitration of fluoranthene, one of the most abundant polycyclic aromatic hydrocarbons (PAH) in diesel fuels, occurs in the laboratory under either electrophilic or free‐radical conditions to give nitro‐PAH. 3‐Nitrofluoranthene (3‐NF) is the major product under electrophilic ionic conditions while 2‐nitrofluoranthene (2‐NF) is the major product under free‐radical nitration conditions. The free‐radical nitration of fluoranthene also yields 1,2‐ and 1,3‐dinitrofluoranthene (1,2‐DNF and 1,3‐DNF). Nitration on the 3‐position of fluoranthene enhances the mutagenic potency more strongly than on the 2‐position. Thus, 3‐NF is a more potent mutagen than 2‐NF and 1,3‐DNF is more potent than 1,2‐DNF, an isomer with one near coplanar nitro group and one nitro group substantially out of plane with the fluoranthene skeleton, when tested against Salmonella typhimurium TA98, TA98NR, and TA98/1,8‐DNP 6 . In addition, the activation of these dinitro‐PAH to mutagens does not depend on the “classical nitroreductase” and/or O‐acetylase, suggesting that they are activated via different pathways. Despite the fact that 3‐NF and 1‐phenyl‐4‐nitronaphthalene (1‐P‐4NN), a non‐planar analog of 3‐NF, have virtually identical reduction potentials, their mutagenic potencies differ by three orders of magnitude. This finding suggests that when nitro‐PAH of varying steric requirements are compared, the reduction potential may not predict mutagenic potency as well as had been previously suggested.