Bleocin

Names

[ Name ]:
Bleocin

[Synonym ]:
(3-{[(2'-{(5S,8S,9S,10R,13S)-15-{6-Amino-2-[(1S)-3-amino-1-{[(2S)-2,3-diamino-3-oxopropyl]amino}-3-oxopropyl]-5-methyl-4-pyrimidinyl}-13-[{[(2R,3S,4S,5S,6S)-3-{[(2R,3S,4S,5R,6R)-4-(carbamoyloxy)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}(1H-imidazol-5-yl)methyl]-9-hydroxy-5-[(1R)-1-hydroxyethyl]-8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,
BLM
Bleomycin
bleomicin
BLEO
BLEOMYCIN SULPHATE
BLEXANE
Bleocin
Blenoxane

Biological Activity

[Description]:

Bleomycin is a glycopeptide antibiotic. Bleomycin has potent antitumour activities against a range of lymphomas, head and neck cancers and germ-cell tumours. Bleomycin can be used for the research of cancer and chemotherapy[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

[In Vitro]

Bleomycin (0-4 mU/mL; 1 h) induces double-strand break in V79 cells[2]. Bleomycin (0-1 mU/mL; 1 h) reduces migration of DNA from S-phase cells[2]. Bleomycin (0-3 μg/mL; 1 h) induces chromatid aberrations in G2 cells[3].

[In Vivo]

Bleomycin (1 mg and 10 μg; retro-orbitary sinus injection once) affects cells in mitosis, induces apoptosis in tumor models[4]. Animal Model: C57Bl/6 mice with LPB and B16F0 tumours[4] Dosage: 1 mg and 10 μg Administration: Retro-orbitary sinus injection; 1 mg and 10 μg once Result: Decreased in the fraction of cells in mitosis in both tumours, induced cell apoptosis after the electric pulses delivery, inceased the amount of atypical cells in LPB tumours.

[References]

[1]. Chen J, Stubbe J. Bleomycins: towards better therapeutics. Nat Rev Cancer. 2005;5(2):102-112.

[2]. Olive PL, et al. Detection of DNA double-strand breaks through the cell cycle after exposure to X-rays, bleomycin, etoposide and 125IdUrd. Int J Radiat Biol. 1993 Oct;64(4):349-58.

[3]. Allio T, Preston RJ. Increased sensitivity to chromatid aberration induction by bleomycin and neocarzinostatin results from alterations in a DNA damage response pathway. Mutat Res. 2000 Sep 20;453(1):5-15.

[4]. Mekid H, et al. In vivo evolution of tumour cells after the generation of double-strand DNA breaks. Br J Cancer. 2003 Jun 2;88(11):1763-71.

Chemical & Physical Properties

[ Molecular Formula ]:
C₅₅H₈₅N₁₇O₂₅S₄

[ Molecular Weight ]:
1415.551

[ Exact Mass ]:
1414.518433

[ PSA ]:
794.66000

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: EC5988000

CHEMICAL NAME :: Bleomycin

CAS REGISTRY NUMBER :: 11056-06-7

LAST UPDATED :: 199706

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Standard Draize test

ROUTE OF EXPOSURE :: Administration into the eye

SPECIES OBSERVED :: Rodent - rabbit

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 351 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - fibrosing alveolitis Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Human

DOSE/DURATION :: 418 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - fibrosing alveolitis Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >200 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 - rat

DOSE/DURATION :: 168 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 :: 168 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 :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/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 :: 35 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 188 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 :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 53 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 :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 270 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intratracheal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 14 mg/kg

TOXIC EFFECTS :: Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 158 mg/kg/5W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 88200 ug/kg/9D-I

TOXIC EFFECTS :: Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 40 mg/kg/4W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 160 mg/kg/4W-I

TOXIC EFFECTS :: Behavioral - food intake (animal) Lungs, Thorax, or Respiration - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 6875 ug/kg/41D-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure) Skin and Appendages - hair Skin and Appendages - nails

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 11 mg/kg/41D-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure) Skin and Appendages - hair Skin and Appendages - nails

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 44 mg/kg/30D-I

TOXIC EFFECTS :: Cardiac - cardiomyopathy including infarction Kidney, Ureter, Bladder - changes primarily in glomeruli Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 200 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: DNA inhibition

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Mammal - cattle Sperm

DOSE/DURATION :: 100 mg/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 326,185,1995 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,134,1987 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,97,1981 IARC Cancer Review:Group 2B IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,134,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4340 No. of Facilities: 356 (estimated) No. of Industries: 1 No. of Occupations: 8 No. of Employees: 8140 (estimated) No. of Female Employees: 5555 (estimated)

Safety Information

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
46-40

[ Safety Phrases ]:
53-36/37-45

[ WGK Germany ]:
3

[ RTECS ]:
EC5991990