title: Mutagenicity of nitro-azabenzo[a]pyrene and its related compounds.
abstract: The mutagenicity of nitrated benzo[a]pyrene (BP) and the related compounds, 1- and 3-nitrobenzo[a]pyrene (NBP), 1- and 3-nitro-6-cyanobenzo[a]pyrene (N-6-CBP), 1- and 3-nitro-6-azabenzo[a]-pyrene (N-6-ABP), 1- and 3-nitro-6-azabenzo[a]-pyrene-N-oxide (N-6-ABPO) and 1,6- and 3,6-dinitrobenzo[a]-pyrene (DNBP), was investigated. The mutagenic activities of 3-N-6-CBP and 3-N-6-ABP were 117 and 76 times, respectively, that of 3-NBP. In addition, 3,6-DNBP was more mutagenic than 1,6-DNBP. It is suggested that the mutagenic activation differs with the position of NO2 substitution in the chemical structure. A nitro derivative with NO2 substitution at the 3 position of the aromatic ring of BP was more mutagenic than that with the substitution at the 1 or 6 position. The reducibility of DNBPs was then determined by detecting 1- or 3-amino-6-nitrobenzo[a]pyrene (A-6-NBP), a metabolite of DNBP; 3,6- and 1,6-DNBP were reduced to 3- and 1-A-6-NBP at frequencies of 958 +/- 26 and 79 +/- 8, respectively, pmole per mg of protein, when the compound was incubated anaerobically with rat liver S9 mix at 37 degrees C for 15 min. NO2 substituted at the 3 position of the aromatic ring of BP was readily reduced by a microsome enzyme to form an amino derivative. The result suggests that these compounds have a structure-activity relationship between mutagenicity and NO2 substitution of BP.
authors.affiliation: Fukuoka Environmental Research Center, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sera
authors.forename: K
authors.initials: K
authors.lastname: Fukuhara
authors.forename: N
authors.initials: N
authors.lastname: Miyata
authors.forename: K
authors.initials: K
authors.lastname: Horikawa
authors.forename: H
authors.initials: H
authors.lastname: Tokiwa
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity*; D001580:Benzopyrenes / Q000737:chemistry / Q000633:toxicity; D015394:Molecular Structure; D009152:Mutagenicity Tests; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D001580:Benzopyrenes; D001564:Benzo(a)pyrene; C042055:3-nitrobenzo(a)pyrene; C040217:1-nitrobenzo(a)pyrene