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Metabolic Activation of Aromatic Amines and Amides and Interactions with Nucleic Acids
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
A typical example of activation of a carcinogenic nitro compound through reduction is 4-nitroquinoline-1-oxide (4-NQO). This compound is reduced to 4-hydroxylamino-quinoline-1-oxide, a strong carcinogen for s.c. tissue and for the skin. A summary of chemical, metabolic, and various biological studies with 4-NQO and related compounds has been made by Endo et al.73
Synergistic Combinations of Hyperthermia and Inhibitors of Nucleic Acids and Protein Synthesis
Published in Leopold J. Anghileri, Jacques Robert, Hyperthermia In Cancer Treatment, 2019
Kessel and Belton80 related the mechanism of action of the Nbf series to a well-studied molecule, 4-nitroquinoline-1-oxide. The effects of this latter compound on Escherichia coli and human Xeroderma pigmentosum cells were found to mimic closely the DNA damage caused by UV radiation.85 As already indicated (Section III of this chapter), hyperthermia has been shown to inhibit DNA repair after damage by UV and ionizing radiation or bleomycin treatment.29,71,72 Since Nbf-Cl has been shown to alkylate a specific thiol of E. coli RNA polymerase, thereby inducing a conformational change and impairing RNA chain elongation,86 a similar mode of action may be assumed in the cell line 114A. Such a mechanism in combination with the postulated effects of hyperthermia on DNA and RNA repair could account for the synergism observed.
Familial Polyposis Coli: A Model for The Study of Promotion and Transformation
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Two GS cell strains were separately treated with N-methyl-N-nitroso-nitroguanidine (MNNG) (1 µg/mℓ) and 4-nitroquinoline-1-oxide (4NQO) (0.1 µg/mℓ) for 24 hr and maintained on TPA (0.1 µg/mℓ) for approximately 6 months. These cultures differed from similarly treated cells described above in that the TPA was removed from media when cells lacked growth potential or were cytotoxic. However, as soon as the cells recovered, the same concentration (0.1 µg/mℓ) of TPA was added again. Transformation properties were judged by visualizing morphological alterations in the cells by growth in soft agar (0.3%) and by intradermal inoculations of 5 to 10 × 106 cells in athymic nude mice. The mice were further immunosuppressed by antilymphocyte serum treatment (0.1 mℓ per mouse) intraperitoneally for 3 weeks.
In vitro mutagenicity and genotoxicity of raw and simulated leachates from plastic waste dumpsite
Published in Toxicology Mechanisms and Methods, 2019
Okunola A. Alabi, Adewale A. Sorungbe, Yetunde M. Adeoluwa
The tester strain E. coli PQ37 was obtained from EBPI (Mississauga, Canada). The SOS chromotest was performed without metabolic activation as described by Quillardet and Hofnung (1985) with modifications provided by Kevekordes et al. (1999) and Alabi et al. (2014). The sample concentrations of 0.63, 1.25, 2.50, 5.00, and 10.00% (v/v, leachate/dimethyl sulfoxide) were considered for each of the raw and simulated leachates in four replicates. A 600-mL volume of an appropriate overnight culture dilution was added to a tube containing 20 mL sample volume and incubated with agitation for 2 h at 37 °C and subsequently centrifuged at 700 g for 20 min. The supernatant was discarded, and the bacterial pellets were resuspended with 200 mL of SOS Chromogen (p-nitrophenyl phosphate (PNPP), Boehringer Mannheim, Laval, Canada; CAS no. 4264-83-9) for alkaline phosphatase (AP) and 5-bromo-4chloro-3-indolyl-b-d-galactopyranoside (X-gal, Vector Biosystems, Toronto, Canada; CAS no. X100) for β-galactosidase (β-gal). Plates were re-incubated (10 min for AP and 60 min for β-gal), after which optical density (OD) readings were taken at 620 nm (β-gal) and 405 nm (AP). 4-Nitroquinoline 1-oxide (4-NQO) was used as positive control. AP reduction factors (RFs), β-gal induction factors (IFs), and corrected induction factors (CIF = IF/RF) were calculated as described by Legault et al. (1996): 1996).
Effectual nanotherapy against oral squamous cell carcinoma
Published in Drug Development and Industrial Pharmacy, 2021
Rituraj Bharadwaj, Subhash Medhi
In the current study, to check the efficacy of the developed nanoformulation we have simulated the oral cancer pathology in animal model by using 4-nitroquinoline-1-oxide. To assess the efficacy of the SLN alone or in combination, the in vivo study was performed in the developed animal model. The formations of lesion in the epithelial region of the tongue in animals were investigated after a period of 16 weeks of induction with 4-nitroquinoline-1-oxide. After confirming visually for the development of OSCC, we started the treatment phase. Although the treatment phase was continued for a period of 4 weeks, but to check the potency of the treatment, the animals were checked after completion of 2nd week treatment and after 4th week from the initiation of the treatment.
Investigation of in vivo unscheduled DNA synthesis in rabbit corneas following instillation of genotoxic agents
Published in Cutaneous and Ocular Toxicology, 2021
Haruna Tahara, Shingo Nemoto, Yoshinori Yamagiwa, Yu Haranosono, Masaaki Kurata
In this study, we investigated the induction of UDS in the corneal epithelium after single eye-drop instillation of genotoxic agents. We used rabbits in this study because they have been commonly used in ocular toxicity studies [22,23] and UDS has been observed in rabbit corneal epithelium after UV irradiation [19]. In this study, we used well-known genotoxic agents (i.e. 1,1′-dimethyl-4,4′-bipyridinium dichloride (paraquat); acridine orange; and ethidium bromide [24,25]) as the test compounds. In addition, we also evaluated acrylamide and 4-nitroquinoline 1-oxide (4-NQO) [26,27] as additional genotoxic agents in the same manner.