硫酸博莱霉素

Bleomycin sulfate是具有有效抗肿瘤活性的DNA合成抑制剂。

信号通路 >> 抗感染 >> 细菌

信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成

研究领域 >> 癌症

DNA/RNA Synthesis[1]

博莱霉素(BLM)被选为人淋巴细胞中研究最好的微核(MN)诱导剂,具有不同的遗传毒性机制。最常见的博来霉素诱导的DNA损伤是单链和双链断裂和单个apuinic/apyrimidinic位点。同时博来霉素是真正的放射性模拟化合物,几乎完全类似于电离辐射的遗传效应[1]。硫酸博来霉素对UT-SCC-19A细胞系的IC50值为4.0±1.3nM。 UT-SCC-12A和UT-SCC-12B对博来霉素(BLM)更具抗性; IC50值分别为14.2±2.8 nM和13.0±1.1 nM [2]。与对照培养物相比,博来霉素(BLM)诱导异常细胞(即,显示至少一种像差的细胞)的百分比和每个细胞的染色体畸变频率显着增加(p <0.05)[3]。

与博来霉素(In-111-BLMC)组合的短程β发射放射性核素是SCC中的肿瘤靶向剂。在35天内,裸鼠体重增加2.8±0.6g。在肿瘤接种后25和35天,肿瘤体积分别为111±51mm 3和874±577mm 3。计算的倍增时间为3.86±0.76天。 SCC细胞系表现出对博来霉素的不同敏感性。我们的SCC肿瘤异种移植模型显示适合使用In-111-BLMC的放射化学治疗研究的快速生长。 In-111-BLMC在体内的摄取与增殖活性成正比,并且可以通过动物模型剂量计算预测具有高结合能力的肿瘤[2]。在博来霉素(BLM)处理后第7天和第14天,TGF-β1的信号显着强于对照组。在治疗后28天,TGF-β1信号稍微变弱。在博来霉素加Dex组的第7天和第14天,TGF-β1的信号也强于对照组。然而,在第28天,TGF-β1信号变弱并且比对照组的水平稍强。通过比较平均IOD值[4]给出所有结果。

ADIPO-P2细胞在补充有20％胎牛血清，青霉素（100U / mL）和链霉素（100μg/ mL）的D-MEM高葡萄糖培养基中于37℃和5％CO 2气氛中生长。在含有1.5×10 5个细胞/ mL的TC25 Corning烧瓶中将细胞培养为单层。对于每个实验，设置两个烧瓶，一个用于对照，一个用于处理的培养物。在生长的对数期期间，用30分钟的2.5μg/ mL博来霉素（溶于无菌0.9％NaCl）脉冲处理ADIPO-P2细胞。对照培养物平行设置但不暴露于博来霉素。在用博来霉素进行脉冲处理结束时，用Hank's平衡盐溶液洗涤细胞两次，并用新鲜培养基保持培养直至收获。在5次传代或处理后的传代培养期间，细胞连续维持在培养物中。每当培养物汇合时（大约4×10 5个细胞/ mL培养基）进行亚培养。为了估计细胞生长，在传代培养时通过胰蛋白酶消化收集细胞，用0.4％台盼蓝染色约200μL的等分试样，并测定活细胞（未染色的细胞）的数量[3]。

将小鼠[4]将60只CD-1小鼠随机分成以下3组（每组n = 20）：盐水;博莱霉素 - 水;博来霉素加地塞米松（Dex）。盐水组中的小鼠气管内注射2mL / kg盐水;其他患者气管内注射博来霉素（5 mg / kg，2 mL / kg，生理盐水）。在博来霉素处理后24小时，通过管饲法给予小鼠0.45mg / kg /天DEX。用博来霉素或盐水气管内注射的那天指定为第0天。

[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.

放线菌酮 | 放线菌素D | 嘌呤霉素二盐酸盐 | G-418 硫酸盐 | 衣霉素 | 潮霉素B | Alpha-毒伞肽 | 盐霉素 | 茴香霉素 | 阿维巴坦钠 | 硫酸新霉素 | SCR7 | 法硼巴坦 | CX-5461 | 甲氧西林钠

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)