4-Nitroquinoline 1-oxide

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4-Nitroquinoline 1-oxide
NQO structure.png
Identifiers
CAS number 56-57-5 YesY
PubChem 5955
ChemSpider 5740 YesY
KEGG C03474 YesY
ChEBI CHEBI:16907 YesY
ChEMBL CHEMBL127655 YesY
Jmol-3D images Image 1
Properties
Molecular formula C9H6N2O3
Molar mass 190.16 g mol−1
Appearance yellow-brown crystals or powder
Melting point 26-28°C
Boiling point 237-243 °C
Solubility in water slightly
Hazards
Flash point 101 °C
Autoignition temperature 400 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Infobox references

4-Nitroquinoline 1-oxide (also known as 4-NQO, 4NQO, 4Nqo, NQO and NQNO) is a quinoline derivative and a tumorigenic compound used in the assessment of the efficacy of diets, drugs, and procedures in the prevention and treatment of cancer in animal models. It induces DNA lesions usually corrected by nucleotide excision repair.

General[edit]

4-nitroquinoline 1-oxide (4NQO) is a quinoline, a carcinogenic and mutagenic chemical. Quinolines, like 4NQO, possess a heterocyclic aromatic structure and the same basic chemical formula of C9H7N [1]. 4NQO may naturally occur in the environment but is typically manufactured for research purposes [2]. 4NQO is known to mimic the biological effects of ultraviolet light on various organisms [3]. Both 4NQO and its reduced metabolite 4-hydroxyaminoquinoline 1-oxide (4HAQO) bind covalently to cellular macromolecules such as nucleic acids and proteins [4].

4NQO may induce DNA damage through the production of reactive oxygen species thought to arise from enzymatic reduction of its nitro group, although its exact mechanism is unknown [5]. 4NQO’s reactive oxygen species may serve as a byproduct of DNA damage or signaling molecule from damage [6]. In response to damage from 4NQO, cells attempt to repair and initiate a transcriptional response to detoxify the cell from 4NQO and its metabolites [7].

Technical[edit]

DNA damage by 4NQO is a potent model. 4NQO induces DNA lesions usually corrected by nucleotide excision repair. 4NQO’s four electron reduction product, 4-hydroxyaminoquinoline 1-oxide (4HAQO), is believed to be a carcinogenic metabolite of 4NQO. When 4NQO is metabolized to its electrophilic reactant, selyl-4HAQO, it reacts with DNA to form stable quinolone monoadducts considered responsible for its mutagenicity and genotoxicity [8].

The stable quinolone monoadducts oxidize to form 8-hydroxydeoxyguanosine (8OHdG), which, if left unrepaired, lead to transversions of guanines to thymines, which are nucleotides in DNA. Despite the direct mutagenic properties of 4HAQO, it is less toxic than 4NQO, indicating that metabolism of 4NQO produces other reactive chemicals such as anion radical metabolites [9].

File:4NQO Metabolites.jpg
4NQO Metabolites

Yeast species have been used to map polymorphic regions in response to 4NQO, identifying the polymorphic transcription factor Yrr1. Yrr1 confers 4NQO resistance to wild-type S. cerevisiae yeast, binding upstream from core genes well-known to regulation drug response [10]. Yrr1 shifts cellular response in resistance to 4NQO and rates of respiration [11].

References[edit]