甲醛和二甲苯联合染毒对小鼠骨髓细胞遗传毒性研究

Joint Effect of Formaldehyde and Xylene on Mouse Bone Marrow Cells

目的探讨甲醛和二甲苯联合染毒对小鼠骨髓细胞的遗传毒性作用。方法将78只健康清洁级昆明小鼠,按体重随机分为13组,分别为低剂量甲醛染毒组(5 mg/kg)、中剂量甲醛染毒组(10 mg/kg)、高剂量甲醛染毒组(20mg/kg)以及生理盐水(0.01 ml/g)对照组;低剂量二甲苯染毒组(50 mg/kg)、中剂量二甲苯染毒组(100 mg/kg)、高剂量二甲苯染毒组(150 mg/kg)以及花生油(0.01 ml/g)对照组;低剂量联合染毒组(2.5 mg/kg甲醛+25 mg/kg二甲苯)、中剂量联合染毒组(5 mg/kg甲醛+50 mg/kg二甲苯)、高剂量联合染毒组(10 mg/kg甲醛+75 mg/kg二甲苯)以及生理盐水+花生油(体积比1∶1)对照组;环磷酰胺(40 mg/kg)作为微核试验阳性对照组。每组6只,雌雄各半。采用腹腔注射方式染毒,每天1次,连续7 d。染毒结束次日处死小鼠,采用微核试验和彗星试验检测骨髓细胞的遗传毒性作用。结果甲醛、二甲苯单独或联合染毒均可引起小鼠骨髓细胞微核率增高(P<0.05),且微核率随着染毒剂量的增加而上升。甲醛与二甲苯联合染毒组微核率高于各自单独染毒组,在高剂量联合染毒组尤其明显(P<0.05)。甲醛、二甲苯单独或联合染毒均可使小鼠骨髓彗星细胞尾部DNA含量及尾矩增加,且高剂量组尤其明显(P<0.05);二者在较低剂量联合染毒时便致彗星细胞尾部DNA含量及尾矩较甲醛和二甲苯单独染毒组有所增加(P<0.05);且随着染毒剂量的升高,联合染毒毒性作用明显上升。结论甲醛、二甲苯染毒对小鼠骨髓细胞具有遗传毒性作用,二者联合染毒可能存在协同毒性效应。

Objective To explore the joint effect of formaldehyde and xylene on mouse bone marrow cells. Methods A total of 78 healthy and clean Kunming mice were divided into 13 groups according to the weight, low dose of formaldehyde （5 mg/kg）, moderate dose （10 mg/kg）, high dose （20 mg/kg） as well as a control group with normal saline （0.01 ml/g）; and low dose of xylene （50 mg/kg）, moderate dose （100 mg/kg）, high dose （150 mg/kg） as well as a control group with peanut oil （0.01 ml/g）; and low dose of joint exposure （2.5 mg/kg formaldehyde plus 25 mg/kg xylene）, moderate dose （5 mg/kg formaldehyde plus 50 mg/kg xylene）, high dose （10 mg/kg formaldehyde plus 75 mg/kg xylene） as well as a control group with normal saline plus peanut oil （the volume ratio is 1：1）; The mice were exposed to formaldehyde and xylene by peritoneal injection for seven days, once a day. The micronucleus test and comet assay were used. Results Formaldehyde and xylene could significantly increase the micronucleus rate of mouse bone marrow cells （P〈0.05） with a dose-dependent manner; the micronucleus rate of joint exposure of xylene and formaldehyde was higher than that of independent exposure, it was significant in the group of high dosage of joint exposure （P〈0.05）. The independent or joint exposure of xylene and formaldehyde could increase the tail DNA content of the comet cells and tail moment. The joint exposure at low dosage could cause larger tail DNA content of the comet cells and tail moment compared with the independent exposure. Conclusion Formaldehyde and xylene have a genetic toxicity to mouse bone marrow cells and the joint exposure has a synergistic toxic effect.