N,N'-Dinitrosopiperazine

N,N'-Dinitrosopiperazine (1,4-Dinitrosopiperazine; DNP) is a carcinogen with specificity for nasopharyngeal epithelium and facilitates NPC metastasis. N,N'-Dinitrosopiperazine regulates multiple signaling pathways through protein phosphorylation, including LYRIC at serine 568[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

N,N'-Dinitrosopiperazine (0.5-100 μM; 48 hours) has no inhibitory effects on the labeled 6-10B cells, and LDH activity is not significantly altered by DNP treatment in the 0.5-8 μM concentration range. However, it is cytotoxic from the concentration 10 μM[1]. N,N'-Dinitrosopiperazine (2-8 μM; 24 hours) induces 6-10B cell invasion and motility in a dose-dependent manner. At 6 μM, when compares to the control group, DNP increases cell invasion at 421.7% and cell motility is increased by 328.2%[1]. N,N'-Dinitrosopiperazine (6 μM; 24 hours) increases the expression of phospho-LYRIC s568 and LYRIC expression in CNE1 cells[1]. Cell Viability Assay[1] Cell Line: The labeled 6-10B cells Concentration: 0.5, 1, 2, 4, 6, 8, 10, 20, 40, 80, or 100 μM Incubation Time: 48 hours Result: Had no inhibitory effects at the concentration 0-8 μM. Western Blot Analysis[1] Cell Line: The NPC cell line CNE1 Concentration: 6 μM Incubation Time: 24 hours Result: Increased phospho-LYRIC s568 and LYRIC expression.

N,N'-Dinitrosopiperazine (injected into the tail veins; 40 mg/kg; 30 days) inhibits cell motility and invasion, and facilitates NPC metastasis in vivo. From a IHC result, Phospho-LYRIC expression is higher in the metastatic tumors of DNP-treated mice than in those of the untreated control mice[1]. Animal Model: BABL/c nude mice injected with labeled 6-10B cell suspensions (1 × 104 cells) with or without DNP(40 mg/kg)[1] Dosage: 40 mg/kg Administration: Injected into the tail veins; 30 days Result: Induced LYRIC phosphorylation at serine 568 associated with NPC metastasis in vivo.

[1]. Damao Huang, et al. Identification of Novel Signaling Components in N,N'-dinitrosopiperazine-mediated Metastasis of Nasopharyngeal Carcinoma by Quantitative Phosphoproteomics. BMC Cancer. 2014 Apr 5;14:243.

DATA ITEMS CITED :

38

MOLECULAR FORMULA :

C4-H8-N4-O2

MOLECULAR WEIGHT :

144.16

WISWESSER LINE NOTATION :

T6N DNTJ ANO DNO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1040 mg/kg/1Y-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1070 mg/kg/53W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

140 mg/kg female 15-21 day(s) after conception

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Blood - leukemia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1568 mg/kg/28W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

720 mg/kg/72W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1800 mg/kg/64W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1100 mg/kg/110W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2250 mg/kg/50W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

7300 mg/kg/52W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

560 mg/kg/10W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1086 mg/kg/69W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Brain and Coverings - tumors Gastrointestinal - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

5280 mg/kg/44W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1120 mg/kg/20W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1680 mg/kg/30W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Sense Organs and Special Senses (Olfaction) - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

140 mg/kg

SEX/DURATION :

female 15-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

400 mg/kg

SEX/DURATION :

lactating female 20 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

TYPE OF TEST :

Specific locus test

TYPE OF TEST :

DNA damage

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Host-mediated assay

TEST SYSTEM :

Rodent - mouse Bacteria - Salmonella typhimurium

DOSE/DURATION :

10 mg/kg

REFERENCE :

CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 37,4572,1977