Nitrochin targets DNA, forming adducts with adenine and guanine bases. These DNA adducts lead to mutations and DNA damage, contributing to its carcinogenic properties. The compound is used as a chemical carcinogen in animal models to induce tumors, particularly tongue cancer in mice when administered in drinking water.

Nitrochin demonstrates in vitro activity by forming DNA adducts and inducing DNA damage. It induces oncostatin-M (OSM) in esophageal cells. The compound's carcinogenic activity is used in research to study DNA repair mechanisms and cancer development.

In vivo activity of nitrochin has been demonstrated as a chemical carcinogen in animal models. When administered at 100 µg/mL in drinking water, it induces tongue cancer in mice. The compound is used in cancer research to study tumorigenesis, DNA repair, and cancer prevention strategies.

In vitro enzyme assays for nitrochin are not typically performed, as the compound is used as a chemical carcinogen rather than as a pharmacologically active compound. Its interactions with DNA can be assessed using DNA adduct formation assays or by measuring DNA damage markers.

In vitro cellular assays for nitrochin involve treating cells with the compound and measuring DNA damage, mutagenesis, or cell transformation. The compound's ability to induce DNA adducts and mutations is assessed using assays such as the Ames test, comet assay, or by measuring mutation frequencies.

In vivo animal experiments for nitrochin involve administering the compound to mice, typically in drinking water at 100 µg/mL, to induce tongue cancer. Tumor development is monitored over time, and the compound is used to study cancer prevention and treatment strategies.

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.

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Pharmacokinetic data for nitrochin indicate that it is administered orally in drinking water for cancer induction studies. The compound is absorbed and distributed to target tissues where it forms DNA adducts. Its metabolism and elimination properties are consistent with those of quinoline derivatives.

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.

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Toxicological data for nitrochin indicate that it is a chemical carcinogen. It forms DNA adducts and induces DNA damage, leading to mutagenesis and tumorigenesis. The compound should be handled with extreme caution using appropriate safety protocols to prevent exposure.

[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.

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Nitrochin (4-NQO) (CAS#: 56-57-5) has the molecular formula C9H6N2O3 and a molecular weight of 190.16. It is also known as 4-Nitroquinoline 1-oxide, 4-Nitroquinoline oxide, and 4-NQO. The compound is a chemical carcinogen used in cancer research.

C9H6N2O3

190.16

190.037

56-57-5

Nitrochin; 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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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