Barrera Escorcia E, Velasco Lezama R, Muñoz Torres A, Ortíz Monroy M V, Fregoso Padilla M, Martínez Aguilar J, Castillo Padilla I, Vargas Vera A
Laboratorio de Biorregulación, Universidad Nacional Autónoma de México-Iztacala, Edo. de México, México.
Sangre (Barc). 1997 Oct;42(5):357-62.
To set up the experimental conditions to induce aplastic anaemia in rats by oral and subcutaneous administration of benzene.
6 groups with 6 male Wistar rats weighting 150 g each were formed. Each group with different conditions; 3 of them as experimental groups: 1) ES group (benzene 2 mL/Kg supplied subcutaneously), 2) EOI and 3) EOII groups (benzene 1.14 and 2 mL/Kg supplied orally); and 3 groups as control: 4) TS and 5) TO groups (supplied only with the vehicle subcutaneously. and orally, respectively) and 6) C group without treatment. Benzene was supplied during four weeks. Blood counts were done at 0, 15 and 30 days of treatment. EOI and EOII treatment was interrupted because of a severe damage to rats and the other groups except TO group continued until 60 days. When the treatment ended haematological determinations continued for 60 days every two weeks including osmotic fragility test and bone marrow smears in order to observe permanent changes.
The rats treated with benzene 4 weeks showed a reduction in concentration of haemoglobin, bleeding of nasal and gastric mucosae, thrombocytopenia, microcytosis and macrocytosis in EOI and EOII groups respectively. The animals treated with benzene 60 days (ES) showed persistent reduction in haemoglobin and platelet concentration, macrocytosis and lymphopenia until day 60. On the other hand, the neutrophil concentration kept lower than the controls after day 75. In these animals blast cells and increased peroxidase positive cells were seen in peripheral blood. Also an increased osmotic fragility of erythrocytes was observed and the bone marrow exhibited deep hypocellularity until day 120.
The administration of benzene subcutaneously damaged irreversibly the myeloid progenitor cells, causing permanent reduction in concentration of erythrocytes, platelets and neutrophils. These results are similar to those reported with the inhalatory exposition to benzene. With the method here assayed long periods of treatment and expensive and sophisticated experimental conditions are avoided.
通过口服和皮下注射苯来建立诱导大鼠再生障碍性贫血的实验条件。
将6组,每组6只体重150 g的雄性Wistar大鼠分组。每组条件不同;其中3组为实验组:1)ES组(皮下注射2 mL/Kg苯),2)EOI组和3)EOII组(分别口服1.14和2 mL/Kg苯);3组为对照组:4)TS组和5)TO组(分别皮下和口服仅给予赋形剂)以及6)未处理的C组。苯给药四周。在治疗的0、15和30天进行血细胞计数。由于大鼠严重受损,EOI组和EOII组的治疗中断,除TO组外的其他组持续到60天。治疗结束后,血液学测定每两周持续60天,包括渗透脆性试验和骨髓涂片,以观察永久性变化。
苯处理4周的大鼠在EOI组和EOII组分别表现出血红蛋白浓度降低、鼻和胃黏膜出血、血小板减少、小红细胞症和大红细胞症。苯处理60天(ES组)的动物直到第60天血红蛋白和血小板浓度持续降低、出现大红细胞症和淋巴细胞减少。另一方面,在第75天后中性粒细胞浓度一直低于对照组。在这些动物的外周血中可见原始细胞和过氧化物酶阳性细胞增加。还观察到红细胞渗透脆性增加,直到第120天骨髓呈现严重的细胞减少。
皮下注射苯不可逆地损伤了髓系祖细胞,导致红细胞、血小板和中性粒细胞浓度永久性降低。这些结果与吸入苯暴露所报道的结果相似。采用本实验方法可避免长时间治疗以及昂贵和复杂的实验条件。