Metabolism / Metabolites
YIELDS 4-HYDROXYLAMINOQUINOLINE-N-OXIDE IN RATS; SUGIMURA, T, OKABE, K, & NAGAO, M, CANCER RES, 26. 1717 (1966); IN MICE; KAWAZOE, Y, UEHARA, N, ARAKI, M, & TAMURA, M, GANN, 60, 617 (1969). /FROM TABLE/
... IS RAPIDLY REDUCED BY RAT-LIVER SOL FRACTION. ... RATE OF REDN IN VITRO OF SERIES OF NITROQUINOLINE N-OXIDES CORRELATES WITH THEIR CARCINOGENICITY. SOL ENZYME RESPONSIBLE FOR THIS REDN IS THOUGHT TO BE DT DIAPHORASE, ENZYME (FLAVOPROTEIN) WHICH CATALYZES OXIDN OF NADPH & NADH.

Interactions
EFFECTS WERE STUDIED OF SODIUM CHLORIDE ON PRODUCTION OF GASTRIC CARCINOMAS BY 4-NITROQUINOLINE-1-OXIDE IN MALE WISTAR RATS. NACL GIVEN ALONE HAD NO APPARENT CARCINOGENICITY BUT WHEN ADMIN WITH 4-NITROQUINOLINE-1-OXIDE IT ENHANCED CARCINOGENIC EFFECTS IN STOMACH.
ADMIN OF 4-NITROQUINOLINE 1-OXIDE TO RATS FOLLOWING PRIOR TREATMENT WITH N-METHYL-N'-NITRO-N-NITROSOGUANIDINE RESULTED IN UNDIFFERENTIATED ADENOCARCINOMAS IN 29% OF TUMORS INDUCED IN GLANDULAR STOMACH.
The modifying effect of three doses of DL-alpha-difluoromethylornithine given orally during the post-initiation phase of tongue carcinogenesis initiated by 4-nitroquinoline 1-oxide was studied in male ACI/N rats. Animals were given 4-nitroquinoline 1-oxide at 20 ppm for 8 wk in the drinking water to induce tongue neoplasms. One wk after the stop of 4-nitroquinoline 1-oxide treatment, rats were transferred to the drinking water containing DL-alpha-difluoromethylornithine at concn of 100, 1000, and 2000 ppm for 25 wk. The other groups consisted of rats given 2000 ppm DL-alpha-difluoromethylornithine alone or untreated rats. Thirty four wk after the start of the experiment, all animals were necropsied, and the incidences of neoplasms and preneoplastic lesions in the tongue, polyamine levels in the bloods and tongue tissues, and cell proliferation estimated by the number and area of silver stained nucleolar organizer regions in the tongue epithelium were compared among the groups. Feeding of DL-alpha-difluoromethylornithine at all doses significantly inhibited the incidence of tongue neoplasms compared to the group given 4-nitroquinoline 1-oxide alone. DL-alpha-difluoromethylornithine at levels of 1000 and 2000 ppm significantly reduced the incidence of preneoplastic lesions of the tongue. Results analyzed by the linear regression method suggested a dose dependent inhibition in the incidences of neoplastic and preneoplastic lesions of the tongue with increasing levels of DL-alpha-difluoromethylornithine. Increased levels in polyamines in the blood and tongue tissue were significantly suppressed by the treatment of DL-alpha-difluoromethylornithine. Also, silver stained nucleolar organizer region indices were significantly reduced by the DL-alpha-difluoromethylornithine exposure. These results indicate that increasing levels of DL-alpha-difluoromethylornithine in the drinking water inhibited 4-nitroquinoline 1-oxide induced tongue carcinogenesis in a dose dependent manner and such inhibition was related to reduction in the polyamine levels of blood and tissue and decrease in the cell proliferation.
The modifying effects of indole-3-carbinol and sinigrin on the initiation and post-initiation phases of tongue carcinogenesis induced by 4-nitroquinoline 1-oxide were investigated in male ACI/N rats. Rats were divided into eight groups: group 1 was given 4-nitroquinoline 1-oxide (10 ppm) in the drinking water for 12 wk, starting at 7 wk of age; groups 2 and 3 were given 4-nitroquinoline 1-oxide and fed the diets containing indole-3-carbinol (1,000 ppm) and sinigrin (1,200 ppm) for 14 wk, respectively, starting at 6 wk of age; groups 4 and 5 were given 4-nitroquinolin 1-oxide and then they were fed indole-3-carbinol and sinigrin containing diets for 23 wk, respectively, starting one wk after 4-nitroquinoline 1-oxide exposure; groups 6 and 7 were given indole-3-carbinol and sinigrin alone, respectively, during the experiment; group 8 served as an untreated control. At the termination of the experiment (wk 37), the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) in group 2 (1/15, 7%), group 3 (1/15, 7%), group 4 (3/15, 20%) or group 5 (2/15, 13%) was significantly smaller than that in group 1 (12/17, 71%) (p= 0.0003, p= 0.005 or p= 0.002). No tongue carcinomas developed in rats of groups 2, 3, and 5. Similarly, the incidence of preneoplastic lesions (hyperplasia and dysplasia) of the tongue in group 2 (11/15, 73%), group 3 (10/15, 67%), group 4 (11/15, 73%) or group 5 (10/15, 67%) was significantly lower than tha in group 1 (17/17, 100%) (p= 0.04 or p= 0.02). There were no tongue neoplasms in rats of groups 6, 7, and 8. Administration of indole-3-carbinol and sinigrin also caused significant decreases in the number and area of silver stained nucleolar organizer regions protein, a new cell proliferation index, of tongue squamous epithelium. Thus, indole-3-carbinol and sinigrin inhibited rat tongue carcinogenesis in both the initiation and post-initiation phases, when administered in these respective phases together with, or following treatment with, 4-nitroquinoline 1-oxide.
For more Interactions (Complete) data for 4-NITROQUINOLINE-N-OXIDE (6 total), 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 plates or needles or yellow solid. (NTP, 1992)
4-nitroquinoline N-oxide is a quinoline N-oxide carrying a nitro substituent at position 4. It has a role as a carcinogenic agent. It is a C-nitro compound and a quinoline N-oxide.
4-Nitroquinoline-1-Oxide is a quinoline derivative with potent tumorigenic activity. 4-nitroquinoline-1-oxide (4-NQO) potentially induces DNA damage by either binding directly to DNA and disrupting replication or through the generation of reactive oxygen species (ROS). 4-NQO is also 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 bind to nucleic acids. It inactivates bacteria but not bacteriophage.

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.)