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Primary and secondary aliphatic nitroalkanes RR'CHNO2, react with microsomal cytochrome p-450 in the presence of dithionite leading to new complexes with a Soret peak at 455 nm. The formation of these complexes is inhibited completely by CO and partially by metyrapone. However, once formed, their exogenous ligand is not displaced by excess CO. By deoxycholate treatment they are transformed into 423-nm-absorbing cytochrome P-420 complexes, which are spectrally similar to the corresponding RR'CHNO2-derived myoglobin complexes. The 455-nm-absorbing complexes are equally produced from RR'CHNO2 reduction, microsomal NADPH-dependent oxidation of the corresponding hydroxylamine RR'CHNHOH, or interaction of the nitrosodimer (RR'CHNO)2 with reduced cytochrome P-450. All the reported results are consistent with the involvement of a new class of ligands of cytochrome P-450-Fe(II), which are the unstable aliphatic nitrosomonomers RR'CHNO, whose nitroso group is isoelectronic with dioxygen and whose stabilisation results from their strong binding to heme-Fe(II), thus explaining the observed inhibition of the hydroxylating function of cytochrome P-450.
A series of nitroheterocyclic compounds were designed with linkages to melamine or benzamidine groups that are known substrates of the P2 aminopurine and other transporters in African trypanosomes of the brucei group. Several compounds showed in vitro trypanotoxicity with 50% inhibitory concentrations in the submicromolar range. Although most compounds interacted with the P2 transporter, as judged by their ability to inhibit adenosine transport via this carrier, uptake through this route was not necessary for activity since TbAT1-null mutant parasites, deficient in this transporter, retained sensitivity to these drugs. One compound, a melamine-linked nitrofuran, also showed pronounced activity against parasites in mice. Studies into the mode of action of this compound indicated that neither reductive, nor oxidative, stress were related to its trypanocidal activity ruling out a genotoxic effect in T. brucei, distinguishing it from some other, mammalian cell toxic, trypanocidal nitroheterocycles.
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The determination of small amount of chlorine in the atmosphere is carried on ordinarily by omicron-toluidine method at present. However, this method is not recommended because the issued colour is unstable and omicron-toluidine itself belongs in the first group member of the Ordinance on Prevention of Particular Chemical Hazards Substances. Authors recommend 4-nitroaniline method, reported by J. Gabbay etc., because this method is stable and more practical. Although the colour that issued from the reaction of chlorine with 4-nitroaniline is affected by the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed by introducing the sample gas into the layer of H2SO4-52Cr2O7 mixture immersed in glassfiber filter for micro-analysis. In this paper, influence of pH of the issued colour, stability, stream velocity of samplegas and effect of reducing substance are discussed.
Determination of mutagenic activity in bacterial systems has become accepted as an initial step in the evaluation of the carcinogenic potential of new chemicals. In this paper, a bacterial mutagen screening technique is described in which chemicals can be tested in 10 tester strains over a 10,000-fold concentration gradient both with and without metabolic activation. Using this assay, 855 chemicals were tested, and 182 were found to be mutagenic in one or more of the tester strains. Included were 299 chemicals used in chemical manufacturing or laboratory synthesis. Of these, 20% gave a positive response in one or more strains. The high rate of positives undoubtedly reflects the high chemical reactivity of compounds in this group. In contrast, when 261 organic chemicals which were synthesized for evaluation as potential pharmaceutical or agricultural products were tested, only 8% were identified as mutagenic. The Salmonella typhimurium tester strains TA98 and TA1538 proved to be very reliable and efficient in detecting and identifying frame-shift mutagens. TA100 was the most sensitive tester strain, detecting 142 of the 182 mutagens encountered in the study. However, since TA100 detected both base substitution mutagens and frame-shift mutagens, this tester strain was not suitable for the specific identification of base substitution mutagens. Base substitution mutagens were more reliably detected by Escherichia coli tester strains WP2 and WP2 uvrA- than they were by S. typhimurium strains G46 and TA1535. The data obtained when mutagens are tested by the concentration gradient procedures can include (a) the activity spectrum in tester strains, (b) identification as either frame-shift or base substitution mutagens, (c) the minimal concentration at which auxotroph growth is inhibited, and (d) mutagenic potency in terms of minimal concentration at which mutagenicity is observed. The data obtained have been found to be of immediate use. For example, with manufacturing intermediates the data have been combined with other toxicity data and used as a basis for setting safety standards for handling such compounds in the workplace. In addition, positive bacterial mutagenicity data on selected members of new series of organic compounds can serve to alert the chemist early to the possibility that the compounds may possess undesirable toxic properties, particularly carcinogenicity. Also, this type of data should be of great value both in the planning and in the interpretation of other in vitro tests designed to evaluate the potential carcinogenicity in mammals of chemicals found to be positive in bacterial tests.
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