Carcinogen 4-nitroquinoline 1-oxide Research Articles

Repair of DNA Damage in Ultraviolet-Sensitive Cells Isolated from HeLa S3 Cells

ISOMURA, K., NIKAIDO, O., HORIKAWA, iIM., AND SUGAHARA, T. Repair of DNA Damage in Ultraviolet-Sensitive Cells Isolated from HeLa S3 Cells. Radiat. Res. 53, 143-152 (1973). Two ultraviolet-sensitive cell lines, designated S-1M and S-2M, were isolated from the original HeLa 83 cells by the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-ultraviolet light (UV) and 5-bromodeoxyuridine (BUdR)-visible light method. The Do values were 87, 68, and 45 ergs/mm2, and the extrapolation numbers (n) were 1.4, 1.0, and 1.0 for HeLa 83, S-1M, and S-2M cells, respectively. The average initial excision rate of UV-induced thymine dimers in the UV-sensitive cells is approximately one fifth that in HeLa S3 cells. The UV-sensitive cells may appear in the original HeLa S3 population due to the mutagenic action of MNNG. S-2M cells are more sensitive to the carcinogen 4-nitroquinoline 1-oxide (4-NQO) than HeLa S3 cells. However, there are no significant differences in sensitivity to x-irradiation among the three cell lines. The findings indicate that the 4-NQO-induced DNA damage and its repair are similar to that found after UV-irradiation, but different from that found after x-irradiation.

Interaction of 4-nitroquinoline 1-oxide with DNA in radiation-sensitive Bacillus subtilis

Action of the carcinogenic chemical 4-nitroquinoline 1-oxide (4NQO) on DNA was studied in two types of UV-sensitive Bacillus subtilis mutants (Hcr − Exc − Deg − Rec + and Hcr + Exc + Deg + Rec −). The former type of mutant was sensitive to 4NQO and also to its reduced metabolite 4-hydroxyaminoquinoline 1-oxide (4HAQO), but the latter type of mutant was not. The results indicate that the in vivo 4NQO damage to DNA was more susceptible to excision repair than to recombination repair. DNA extracted from 4NQO-treated cells was host-reactivated in the parental strain cells as measured by its transforming activity, but not in the UV-sensitive (Hcr −) cells. The host cell reactivation was not found on free DNA treated with 4HAQO in vitro, indicating that 4HAQO is not the sole active form among metabolites of 4NQO. Induction of DNA single-strand breaks in 4NQO-treated cells was independent of the cellular 4NQO sensitivity. Partial repair of the breaks was found only in the parental strain.

Carcinogenesis in tissue culture X. Rejoining of single-strand breaks in DNA of mammalian cells induced by chemical carcinogens (4-nitroquinoline 1-oxide and its derivative) in vitro

The chemical carcinogens 4-nitroquinoline 1-oxide (4-NQO) and 4-hydroxylaminoquinoline 1-oxide (4-HAQO) can induce single-strand breaks in the DNA of cultured Ehrlich ascites tumor cells. In cells incubated after treatment with these carcinogens most of the DNA fragments can be rejoined. This rejoining process may be related to the malignant transformation of normal cells by treatment in vitro with carcinogenic compounds.

Characterization of respiration-deficient mutant of [formula omitted] lacking cytochromes a and c

A respiration-deficient yeast 58NW-46, which lacked the absorption of cytochromes a and c and showed characteristic absorption maxima at 529 and 557 mμ, was induced by treatment of haploid strain of Saccharomyces cerevisiae with carcinogenic agent 4-nitroquinoline 1-oxide. The mutant was demonstrated as a unique one which contained only cytochrome b 2, since the absorption maxima of mutant cells were identical with those of yeast cytochrome b 2 and the mutant had L-lactate dehydrogenase which was considered to be cytochrome b 2.

Studies on Hydrogen Exchange. X. Tritium-Labeling of Carcinogenic 4-Nitroquinoline 1-Oxide and Related Compounds

Studies on Hydrogen Exchange. X. Tritium-Labeling of Carcinogenic 4-Nitroquinoline 1-Oxide and Related Compounds

Physicochemical Interaction of the Carcinogen 4-Nitroquinoline 1-Oxide and Its Analogues with Purine and Pyrimidine Bases as the Component of Nucleic Acid

Physicochemical Interaction of the Carcinogen 4-Nitroquinoline 1-Oxide and Its Analogues with Purine and Pyrimidine Bases as the Component of Nucleic Acid

Mutagenicity in yeast of nitroquinolines and related compounds

A series of 14 nitroquinolines and hydroxyaminoquinolines, related to the potent water-soluble carcinogen 4-nitroquinoline 1-oxide (4-NQO), were tested for induction of respiratory-deficient mutants in Saccharomyces cerevisiae. Eight quinolines, including 4-NQO and 4-hydroxyaminoquinoline 1-oxide, were mutagenic at concentrations markedly inhibiting growth; remaining compounds were nonmutagenic. Good correlation was demonstrated between mutagenicity of these quinolines and established data on their carcinogenicity, photodynamic activity, free-radical production, and lysogeny.

Reaction mechanism in aromatic heterocyclic compounds. X. Kinetics of the reaction of carcinogenic 4-nitroquinoline 1-oxide and its derivatives with sodium ethoxide.

Basic kinetic data, rate constants, activation energies, and entropies of activation were elucidated for the reactions of 22 kinds of 4-NQO derivatives with sodium ethoxide in anhydrous ethanol by spectroscopic-method. Correlations existed between the rate constants and carcinogenicities, and half-wave reduction potentials. Hammett paramaters were applied to the rate constants, and a linear correlation existed in 6-and 7-substituted derivatives. Interactions of 4-nitro group and 3- or 5-position substituents retarded the rate, but for 2- or 8-position, only bulky substituents such as methyl group interacted with the N-oxide group.

Electronic properties of N-heteroaromatics. XLI. Charge-transfer interactions of the carcinogen 4-nitroquinoline 1-oxide with methylsubstituted benzenes and methylsubstituted aniline derivatives

With the object of examining the π-acceptor property of carcinogenic 4-nitroquinoline 1-oxide, spectrophotometric examination was made on the interaction of the N-oxide compound with a variety of methyl substituted benzenes and anline derivatives. The following results were obtained through analysis of the new absorption bands which appeared in the visible difference spectra of mixed systems of the above derivatives and the N-oxide compound : (1) Absorption maxima of the difference bands shifted toward a longer wavelength region with increasing polarity of the solvents. (2) There was a linear relationship between IP values of the methyl substituted benzenes and aniline derivatives and hv values of the absorption maxima. (3) It was confirmed that complexes of 1 : 1 molar ratio were formed by the interaction. (4) A corresponding relationship was found to exist between K values of the methyl substituted benzene-N-oxide compound complexes and IP values of the substituted benzenes. (5) The K values of the aniline derivative-N-oxide compound complexes were affected markedly by the steric effect of substitutent methyl groups. (6) Analysis of the pH effect indicated that the uonionized species of aniline derivatives were more favorable for the interaction. Based upon these results (1-6), it was presumed that π-π type and n-π type charge transfers were involved in the interaction of 4 -nitroquinoline 1-oxide with methyl substituted benzenes and aniline derivatives. The magnitude of ΔH values was consistent with this presumption. It was also found that the carcinogenic quinoline compound is a stronger π-acceptor than non-carcinogenic 4-nitropyridine 1-oxide.

Electronic properties of N-heteroaromatics. 31. Interaction of the carcinogen 4-nitroquinoline 1-oxide with nicotinamide

A spectrophotometric study was made on the interaction of the carcinogen 4-nitroquinoline 1-oxide (4-NQO) with nicotinamide, and formation of a charge-transfer complex, in which n-electron of the ring nitrogen of nicotinamide is transferred tothe π-system of 4-NQO was presumed from the following results : (1) A new absorption band characteristic of chargetransfer complex was exhibited in the vicinity of 402 mμ in the difference spectra of aqueous mixtures of nicotinamide and 4-NQO vs. 4-NQO. (2) Analysis of the new absorption band through the Benesi-Hildebrand's equation revealed that a complex of 1 : 1 molar ratio was formed. (3) Intensity of the absorption band decreased in acid region below pH corresponding to pKa of nicotinamide. (4) Intensity of absorption band, which was produced around 396 mμ in the difference spectra of mixed system of 1-methylnicotinamide and 4-NQO was not infiuenced by variation of pH. (5) In the case of mixed system of nicotinamide and 4 -nitropyridine 1-oxide, whose electron affinity is smaller than that of 4-NQO, difference band appeared at about 340 mμ, i.e., in the shorter wave length region than that of the NA-4-NQO system. The magnitudes of ε, K, ΔH, and ΔS values were consistent with the above presumption. Examination of solvent effect revealed that the new absorption bands arose from n→π* transition.

N-ヘテロ芳香族の電子的性状 : 第24報 発ガン性物質4-Nitroquinoline 1-Oxideとチアミシとの相互作用 錯体形成および置換反応

Interaction between carcinogenic 4-nitroquinoline 1-oxide (4-NQO) and thiamine has been investigated. When required, we used a model compound which contained a thiazolium or a pyrimidine as part of the thaimine molecule and we found out that either molecular complexation or substitution reaction between 4-NQO and thiamine took place in acid or alkaline region, respectively. The difference spectra of acid mixtures of 4-NQO and thiamine exhibited an absorption maximum in the vicinity of 400 mμ. Spectrophotometric examinations were made on the effects of pH and polarity of solvents upon the complex formation, the molar ratio (1 : 1) and ε, K, and ΔH values of the complex. It was found that the interaction was best explainable in terms of n-π type charge transfer between thiamine and 4-NQO, wherein the pyrimidine moiety of the former acts as electron donor and the latter as electron acceptor. The substitution reaction between 4-NQO and thiamine in alkaline solution was exhibited by the appearance of a new absorption band around 360 mμ region of the spectrum of the mixture as well as by the liberation of nitrite ion from the reaction mixture. Quantitative examination was made on the nitrite ion liberation reaction, and the involvement of thiol group of thiamine and nitro group of 4-NQO was presumed. A chemical structure is proposed for the reaction product, which was separated by paper chromatography. Non-carcinogenic 4-nitropyridine 1-oxide also formed a molecular complex with thiamine in acid medium, but it gave no detectable reaction with the vitamin in alkaline medium.

Interaction of the carcinogen 4-nitroquinoline 1-oxide with protein and aromatic amino acids.

Interaction of the carcinogen 4-nitroquinoline 1-oxide with protein and aromatic amino acids.

Electron spin resonance study on the photoinduced radicals from carcinogenic 4-nitroquinoline 1-oxide.

UV-irradiation of 4-nitroquinoline 1-oxide in solutions, that is, in dioxane, in benzene, and in hexane, induced stable radicals which were investigated by ESR spectroscopy. Hyperfine structures of spectra thus obtained are different from each other depending on the sort of the solvents used. Determination of these radical structures were carried out by help of isotope-containing 4-nitroquinoline 1-oxides and, in particular, the structure of dioxane type radical was proposed, based on spectral changes by isotope replacement.

Electron Spin Resonance Study on the Photoinduced Radicals from Related Compounds to Carcinogenic 4-Nitroquinoline 1-Oxide

UV-irradiation of quinoline 1-oxide derivatives were studied by electron spin resonance technique and 4-nitroquinoline 1-oxide (4-NQO) derivatives except for 3-methyl-4-NQO and 4, 8-dinitroquinoline 1-oxide were found to produce two kinds of stable radicals in dioxane or in benzene. This photochemical behavior was discussed from a view point of radical formation.