Genotoxic activity of two furan analogues of benzo[a]pyrene and their 2-nitro derivatives.
We measured the genotoxic activities in two bacterial tests, the Salmonella/histidine assay (a reverse mutation assay) and the SOS Chromotest (an assay for SOS induction in E. coli), of two pairs of isomeric furan analogues of benzo[a]pyrene: pyreno[1,2-b]furan (R7490) and pyreno[2,1-b]furan (R7692) and their 2-nitro derivatives, 8-nitro-pyreno[1,2-b]furan (R7489) and 8-nitro-pyreno[2,1-b]furan (R7691). We found that: For all 4 compounds, the responses were correlated in the two tests. For the 2-nitro derivatives, R7489 and R7691, the responses were extremely high, reaching SOS-inducing potencies of 5.2 X 10(3) and 10(5)/nmole in the SOS Chromotest and mutagenic potencies of 6.3 X 10(4) and 3.7 X 10(7) revertants/nmole in the Salmonella/histidine assay (strain TA98), respectively; the responses were only slightly decreased in nitroreductase-deficient strains. The responses to the two pyrenofurans were increased in the presence of an "activating mixture" but were still lower than that to benzo[a]pyrene. In contrast to benzo[a]pyrene and pyreno[2,1-b]furan (R7692), pyreno[1,2-b]furan (R7490) also gave a response in the absence of an "activating mixture". (5) Compounds with the oxygen heteroatom within the "bay region" gave lower responses than their isomers with the oxygen heteroatom outside the "bay region".
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001580:Benzopyrenes / Q000494:pharmacology*; D001711:Biotransformation; D004260:DNA Repair / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects*; D005663:Furans / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D009601:Nitroreductases / Q000378:metabolism; D051381:Rats; D013014:SOS Response, Genetics / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D001580:Benzopyrenes; D005663:Furans; D009601:Nitroreductases