Metabolism / Metabolites
In rats, 4-hydroxyaminoquinoline-N-oxide is produced; SUGIMURA, T, OKABE, K, & NAGAO, M, CANCER RES, 26, 1717 (1966); In mice, 4-hydroxyaminoquinoline-N-oxide is produced; KAWAZOE, Y, UEHARA, N, ARAKI, M, & TAMURA, M, GANN, 60, 617 (1969). /Excerpt from Table/ …can be rapidly reduced by rat liver sol components. …The in vitro reduction rate of a series of nitroquinoline-N-oxides is correlated with their carcinogenicity. The sol-enzyme leading to this reduction is thought to be DT dihydroflavinase, an enzyme (flavin protein) that catalyzes the oxidation of NADPH and NADH.

Interactions
The effects of sodium chloride on 4-nitroquinoline-1-oxide-induced gastric cancer development in male Wistar rats were investigated. Sodium chloride alone (NACl) showed no significant carcinogenicity, but its carcinogenicity in the stomach was enhanced when combined with 4-nitroquinoline-1-oxide. Pretreatment of rats with N-methyl-N'-nitro-N-nitrosoguanidine followed by administration of 4-nitroquinoline-1-oxide resulted in 29% of tumors induced in the proventriculus developing into undifferentiated adenocarcinoma. In male ACI/N rats, the regulatory effects of three oral doses of DL-α-difluoromethylornithine were investigated in the early stages of 4-nitroquinoline-1-oxide-induced tongue cancer development. To induce tongue tumors, 20 ppm of 4-nitroquinoline-1-oxide was added to the animals' drinking water for 8 weeks. One week after cessation of 4-nitroquinoline-1-oxide treatment, rats were transferred to drinking water supplemented with DL-α-difluoromethylornithine at concentrations of 100, 1000, and 2000 ppm for 25 weeks. Other groups included rats administered DL-α-difluoromethylornithine alone and untreated rats. Thirty-four weeks after the start of the experiment, all animals were dissected, and the incidence of tongue tumors and precancerous lesions, polyamine levels in blood and tongue tissue, and cell proliferation were assessed by the number and area of silver-stained nucleolar organizing regions (NORs) in tongue epithelial cells. Compared with the group administered 4-nitroquinoline-1-oxide alone, all doses of DL-α-difluoromethylornithine significantly inhibited the incidence of tongue tumors. Concentrations of DL-α-difluoromethylornithine at 1000 ppm and 2000 ppm significantly reduced the incidence of tongue precancerous lesions. Linear regression analysis showed that the incidence of tongue tumors and precancerous lesions decreased in a dose-dependent manner with increasing DL-α-difluoromethylornithine concentration. DL-α-difluoromethylornithine treatment significantly inhibited the increase of polyamine levels in blood and tongue tissue. Furthermore, DL-α-difluoromethylornithine exposure also significantly reduced the silver-stained nucleolar histiocytosis index. These results indicate that increasing DL-α-difluoromethylornithine levels in drinking water inhibited 4-nitroquinoline-1-oxide-induced tongue cancer in a dose-dependent manner, and this inhibition was associated with decreased polyamine levels in blood and tissue and reduced cell proliferation. This study investigated the regulatory effects of indole-3-carbinol and glucosinolates on the initiation and post-initiation phases of 4-nitroquinoline-1-oxide-induced tongue cancer in male ACI/N rats. Rats were divided into eight groups: Group 1, starting at 7 weeks of age, received 4-nitroquinoline-1-oxide (10 ppm) in their drinking water for 12 weeks; Groups 2 and 3, starting at 6 weeks of age, were given 4-nitroquinoline-1-oxide and fed diets containing indole-3-methanol (1,000 ppm) and glucosinolate (1,200 ppm), respectively, for 14 weeks; Groups 4 and 5 were given 4-nitroquinoline-1-oxide first, and then, after one week of exposure to 4-nitroquinoline-1-oxide, were fed diets containing indole-3-methanol and glucosinolate, respectively, for 23 weeks; Groups 6 and 7 were given indole-3-methanol and glucosinolate alone, respectively, during the experiment; and Group 8 served as an untreated control group. At the end of the experiment (week 37), the incidence of tongue tumors (squamous cell papilloma and carcinoma) in groups 2 (1/15, 7%), 3 (1/15, 7%), 4 (3/15, 20%), or 5 (2/15, 13%) was significantly lower than that in group 1 (12/17, 71%) (p = 0.0003, p = 0.005, or p = 0.002). No tongue cancer occurred in groups 2, 3, and 5. Similarly, the incidence of precancerous lesions (hyperplasia and dysplasia) in groups 2 (11/15, 73%), 3 (10/15, 67%), 4 (11/15, 73%), and 5 (10/15, 67%) was also significantly lower than that in group 1 (17/17, 100%) (p = 0.04 or p = 0.02). No tongue tumors were developed in rats in groups 6, 7, and 8. Administration of indole-3-methanol and glucosinolate also significantly reduced the number and area of silver-stained nucleolar tissue protein (a novel marker of cell proliferation) in tongue squamous epithelial cells. Therefore, indole-3-methanol and glucosinolate inhibited the development of tongue cancer in rats at both the initial and late initiation stages, a phenomenon observed when they were co-administered with or after treatment with 4-nitroquinoline-1-oxide. For more complete data on interactions with 4-nitroquinoline-1-oxide (a total of 6), please visit the HSDB record page.

[1]. Mukherjee A, et al. Carcinogen 4-Nitroquinoline Oxide (4-NQO) Induces Oncostatin-M (OSM) in Esophageal Cells. In Vivo. 2023 Mar-Apr;37(2):506-518.
[2]. Han H, et al. 4-NQO induces apoptosis via p53-dependent mitochondrial signaling pathway. Toxicology. 2007 Feb 12;230(2-3):151-63.

Yellowish-brown flaky or needle-like crystals or yellow solid. (NTP, 1992)
4-Nitroquinoline N-oxide is a quinoline N-oxide with a nitro substituent at the 4-position. It is a carcinogen. It is a C-nitro compound and also a quinoline N-oxide.
4-Nitroquinoline-1-oxide is a quinoline derivative with strong tumorigenic activity. 4-Nitroquinoline-1-oxide (4-NQO) can induce DNA damage by directly binding to DNA and disrupting replication or by generating reactive oxygen species (ROS). 4-NQO can also be metabolized to form other mutagenic compounds, such as 8-hydroxy-2'-deoxyguanosine.
A potent mutagen and carcinogen. This compound and its metabolite 4-hydroxyaminoquinoline-1-oxide can bind to nucleic acids. It can inactivate bacteria but not bacteriophages.

C9H6N2O3

190.16

190.037

56-57-5

5955

YELLOW NEEDLES OR PLATES FROM ACETONE

1.4±0.1 g/cm3

387.6±34.0 °C at 760 mmHg

154-156 °C(lit.)

188.2±25.7 °C

0.0±0.9 mmHg at 25°C

1.659

0.92

0

3

0

14

229

0

[O-][N+]1=C([H])C([H])=C(C2=C([H])C([H])=C([H])C([H])=C12)[N+](=O)[O-]

YHQDZJICGQWFHK-UHFFFAOYSA-N

InChI=1S/C9H6N2O3/c12-10-6-5-9(11(13)14)7-3-1-2-4-8(7)10/h1-6H

4-nitro-1-oxidoquinolin-1-ium

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 100 mg/mL (525.87 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)