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9041-93-4 41432-97-7
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9041-93-4

9041-93-4 structure
9041-93-4 structure
Name Bleomycin sulfate
Synonyms Blenmycins
BleoMycin Sufate
BLEMOYCIN SULFATE
Bleomycin (sulfate)
BLENOXANE
MFCD00070310
BLEO
BLEXANE
BLEOMYCIN SULPHATE
Blocamicina
EINECS 232-925-2
Description Bleomycin sulfate is a DNA synthesis inhibitor with potent antitumor activity.
Related Catalog
Target

DNA/RNA Synthesis[1]
In Vitro Bleomycin (BLM) is chosen as the best-studied micronucleus (MN) inducers in human lymphocytes with different mechanisms of genotoxicity. The most frequent Bleomycin-induced DNA lesions are single and double strand breaks and single apuinic/apyrimidinic sites. At the same time Bleomycin is true radiomimetic compound, resembling almost completely the genetic effect of ionizing radiation[1]. The IC50 value of Bleomycin sulfate for UT-SCC-19A cell line is 4.0±1.3 nM. UT-SCC-12A and UT-SCC-12B are both more resistant to Bleomycin (BLM); IC50 values are 14.2±2.8 nM and 13.0±1.1 nM, respectively[2]. Bleomycin (BLM) induces a significant increase in the percentage of aberrant cells (i.e., cells showing at least one aberration) and in the frequency of chromosomal aberrations per cell compare with control cultures 18 h after treatment (p<0.05)[3].
In Vivo A short-range beta-emitting radionuclide combined to Bleomycin (In-111-BLMC) is a tumor-targeting agent in SCCs. Within 35 days the weight of nude mice increases 2.8±0.6g. At 25 and 35 days after tumor inoculations the tumor volumes are 111±51 mm3 and 874±577 mm3, respectively. The calculated doubling time is 3.86±0.76 days. SCC cell lines demonstrate different sensitivity to Bleomycin. Our SCC tumor xenograft model shows a rapid growth proper for radiochemotherapeutic studies using In-111-BLMC. The uptake of In-111-BLMC in vivo has been directly proportional to proliferation activity, and the tumors with high binding capacity could be predicted from animal model dose calculations[2]. At 7 and 14 days after Bleomycin (BLM) treatment, the signal of TGF-β1 is significantly stronger than that of the control group. At 28 days after treatment, the TGF-β1 signal became a little weaker. At 7 and 14 days of Bleomycin plus Dex group, the signal of TGF-β1 is also stronger than that of the control group. However, at 28 days, the TGF-β1 signal become weaker and is a little stronger than the level of control group. All the results are given by comparison of the average IOD value[4].
Cell Assay ADIPO-P2 cells are grown in D-MEM high glucose medium supplemented with 20% fetal calf serum, penicillin (100 U/mL) and streptomycin (100 μg/mL) at 37°C and 5% CO2 atmosphere. Cells are cultured as monolayer in TC25 Corning flasks containing 1.5×105 cells/mL. For each experiment, two flasks are set up, one for the control and one for the treated culture. During the log phase of growth ADIPO-P2 cells are treated with a 30 min pulse of 2.5 μg/mL of Bleomycin (dissolved in sterile 0.9% NaCl). Control cultures are set up in parallel but not exposed to Bleomycin. At the end of the pulse treatment with Bleomycin, the cells are washed twice with Hank's balanced salt solution and kept in culture with fresh culture medium until harvesting. Cells are continuously maintained in culture during 5 passages or subcultures after treatment. Subcultivation is carried out whenever the cultures became confluent (approximately 4×105 cells/mL of culture medium). To estimate cell growth, at the time of subcultivation cells are collected by trypsinization, an aliquot of about 200 μL stained with 0.4% trypan blue, and the number of viable cells (cells not stained) is determined[3].
Animal Admin Mice[4] 60 CD-1 mice are randomly divided into the following 3 groups (n=20 each): saline-water; Bleomycin -water; Bleomycin plus Dexamethasone (Dex). Mice in the saline group are injected intratracheally with 2 mL/kg saline; the others are injected intratracheally with Bleomycin (5 mg/kg, 2 mL/kg in saline). Twenty-four hours after Bleomycin treatment, mice are given by gavage 0.45 mg/kg/d DEX. The day of intratracheal injection with Bleomycin or saline is designated day 0.
References

[1]. Hovhannisyan G, et al. Comparative analysis of individual chromosome involvement in micronuclei induced by mitomycin C and bleomycin in human leukocytes. Mol Cytogenet. 2016 Jun 21;9:49.

[2]. Jaaskela-Saari HA, et al. Squamous cell cancer cell lines: sensitivity to bleomycin and suitability for animal xenograft studies. Acta Otolaryngol Suppl. 1997;529:241-4.

[3]. Paviolo NS, et al. Telomere instability is present in the progeny of mammalian cells exposed to bleomycin. Mutat Res. 2012 Jun 1;734(1-2):5-11.

[4]. Shi K, et al. Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-β, Smad3 and JAK-STAT pathway. Int J Clin Exp Med. 2014 Sep 15;7(9):2645-50.
Melting Point 197ºC (dec)
Molecular Formula C55H85N17O25S4
Molecular Weight 1512.62
PSA 1506.34000
Water Solubility H2O: 20 mg/mL

CHEMICAL IDENTIFICATION

RTECS NUMBER :
EC5991990
CHEMICAL NAME :
Bleomycin, sulfate
CAS REGISTRY NUMBER :
9041-93-4
LAST UPDATED :
199706

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Parenteral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
20 ug/kg
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - cyanosis Skin and Appendages - dermatitis, allergic (after systemic exposure)
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Unreported
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
0.286 units/kg/1D-I
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - fibrosis (interstitial) Lungs, Thorax, or Respiration - acute pulmonary edema
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
240 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 :
86 mg/kg
TOXIC EFFECTS :
Gastrointestinal - hypermotility, diarrhea Kidney, Ureter, Bladder - urine volume increased Skin and Appendages - hair
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
59 mg/kg
TOXIC EFFECTS :
Behavioral - ataxia
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
210 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 - mouse
DOSE/DURATION :
103 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - body temperature decrease
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
74 mg/kg
TOXIC EFFECTS :
Behavioral - ataxia
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
14 mg/kg/68W-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors Tumorigenic - tumors at site of application
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Parenteral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
18 mg/kg/52W-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors Tumorigenic - tumors at site of application
TYPE OF TEST :
TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE :
Parenteral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
36 mg/kg/52W-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors Tumorigenic - tumors at site of application
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
8 mg/kg
SEX/DURATION :
female 6-9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
20400 ug/kg
SEX/DURATION :
female 14 day(s) pre-mating female 1-20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
8700 ug/kg
SEX/DURATION :
female 15-22 day(s) after conception lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
17400 ug/kg
SEX/DURATION :
female 15-22 day(s) after conception lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - live birth index (measured after birth)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
15600 ug/kg
SEX/DURATION :
female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - abortion
TYPE OF TEST :
Specific locus test
TYPE OF TEST :
Dominant lethal test
TYPE OF TEST :
Morphological transformation
TYPE OF TEST :
Unscheduled DNA synthesis

MUTATION DATA

TYPE OF TEST :
Mutation in mammalian somatic cells
TEST SYSTEM :
Rodent - hamster Ovary
DOSE/DURATION :
50 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 135,199,1984 *** 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 - X3576 No. of Facilities: 371 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 15071 (estimated) No. of Female Employees: 10631 (estimated)
Symbol GHS08
GHS08
Signal Word Danger
Hazard Statements H340-H351-H361
Precautionary Statements P201-P280-P308 + P313
Personal Protective Equipment Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes T: Toxic;Xi: Irritant;
Risk Phrases R46
Safety Phrases S53-S36/37-S45
RIDADR NONH for all modes of transport
WGK Germany 3
RTECS EC5991990

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