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In bacteria, 4-nitroquinoline-1-oxide (NQO) causes primarily mutations of the base-substitution type although frameshift mutations are also induced. The adducts formed are presumably recognized by error-prone DNA repair enzymes as evidenced by the much greater activity in plasmid pKM101-bearing taster strains. Although reduction of the nitro group appears to be required for mutagenic activity, this reduction is not catalyzed by the nitroreductase required for the demonstration of the mutagenicity in bacteria of other nitro-containing mutagens (nitrofurans, 2-nitronaphthalene, nitrofluorenes). The reduction of the nitro group appears to be catalyzed by a different nitroreductase. The mutagenicity of the non-carcinogenic 3-methyl-4-nitroquinoline-1-oxide (meNQO) may be related to this newly recognized nitroreductase. It is proposed, further, that the ultimate mutagenic intermediates derived from NQO and MeNQO differ.

Nitrated polycyclic aromatic hydrocarbons, including carcinogens, may be non-mutagenic in microorganisms because bacterial nitroreductases are unable to reduce their nitro function to proximate mutagenic hydroxylamines. This reduction of the nitro moiety can be accomplished chemically in situ using zinc dust. The procedure, which is compatible with the Salmonella mutagenicity assay, was used to generate mutagens from chemicals which otherwise are non-mutagenic even in the presence of microsomal preparations.

The antimicrobial agents nalidixic acid and novobiocin, both inhibitors of DNA gyrase, preferentially inhibit the growth of DNA repair-deficient Escherichia coli, Salmonella typhimurium and Bacillus subtilis. On the other hand, these agents exhibit no demonstrable mutagenicity for S. typhimurium and E. coli even when tested under conditions designed to take the metabolic properties of these agents into consideration. Novobiocin and nalidixic acid are widely used in animal and human medicine and further studies to assess their genetic and carcinogenic potentials appear to be in order.

Organic solvent extracts from airplane emission particulates are mutagenic for Salmonella typhimurium strain TA98. Using Salmonella tester strains deficient in enzymes required for the bioactivation of various nitroarenes, the mutagenicity present in these emissions was ascribed to the presence of nitrated polycyclic aromatic hydrocarbons. Based on the known aircraft particulate emission rates at U.S. airports, and using 1-nitropyrene (1-NP) and 1,8-dinitropyrene (1,8-DNP) as surrogates, it is calculated that at a minimum 7 kg 1-NP and 20 g, 1,8-DNP are emitted daily at a typical U.S. airport.

Nitropyrenes as well as several other nitroarenes and their metabolites exhibit considerable mutagenicity for Salmonella tester strains (TA102 and TA96) which have adenine-thymine base pairs at the mutational target. This finding is unexpected as previous biochemical studies had shown that arylation at the C8 position of DNA-guanine is the only chemically and biologically significant reaction. This conclusion is supported by the extraordinary mutagenic potency of these chemicals in Salmonella strains with guanine at the mutational site (e.g., TA98). The present results indicate that a minor reaction with DNA-adenine may result in the formation of an unusually potent promutagenic DNA adduct.

Strains derived from Salmonella typhimurium LT-2, which are used as tester strains in mutagenicity assays, show significant changes in biochemical phenotypes. The presence of plasmid pKM101 in these strains greatly increases both the frequency of these shifts as well as the spectrum of phenotypes involved. It is suggested that in plasmid-free strains these variations reflect the effects of endogeneously induced mutatons which are amplified in the absence of a functional uvrB gene product. In plasmid-containing strains this genetic drift may be promoted further by the pKM101-coded error-prone DNA repair system. The observation of a plasmid-mediated genetic drift lends support to the suggestion that transposons may contribute to the carcinogenic process.

Allyl chloride (3-chloroprene) is mutagenic for Salmonella typhimurium and it induces gene conversions in Saccharomyces cerevisiae. It also displays DNA-modifying activity for E. coli. This is in contrast to a recent study which reported its lack of genetic activity for Salmonella typhimurium.

The environmental contaminants pyrene, 1-nitropyrene, 1,8-dinitropyrene, fluoranthene, and 3-nitrofluoranthene were exposed to light (greater than or equal to 310 nm) either in DMSO, or following coating onto silica. Under all conditions tested the pyrenyl were less stable than the fluoranthenyl compounds. During irradiation in DMSO or on silica, 1-nitropyrene had half-lives of 1.2 and 6 days, while those of 3-nitrofluoranthene were 12.5 and greater than 20 days, respectively. The photodecomposition of 1,8-dinitropyrene resembled that of 1-nitropyrene with half-lives of 0.7 and 5.7 days. A principle photodecomposition product of 1,8-dinitropyrene was identified as 1-nitropyren-8-ol. It was also found that when the nitroarenes were exposed to light, the loss of compound was associated with a concomitant loss of mutagenicity in Salmonella typhimurium strain TA98. The mechanism of nitrated polycyclic aromatic hydrocarbon decomposition and 1-nitropyren-8-ol formation, and the relevance to the atmospheric disposition of these compounds are discussed.

Two mutagenic metabolites of phenacetin, p -nitrosophenetol and N -hydroxy- p -phenetidine, were tested in S. typhimurium strains TA100, its nitroreductase-deficient derivative TA100NR, and O -acetylase-deficient strains TA100 Tn5-1-8-DNP1011 and -DNP1012 in the presence or absence of an exogenous metabolic activation system. The results indicate that bacterial nitroreductase(s) and O -acetylase(s), shown to be involved in the conversion of certain nitroarenes, are not required for the intrabacterial activation of the two phenacetin metabolites to bacterial mutagens. In view of the low reactivity of nitrosoarenes towards nucleophiles at neutrality, the mechanism by which they exert such a high mutagenic effect in S. typhimurium strains remains to be clarified, but is discussed.