甲醛和甲苯联合染毒对雄性小鼠生殖与遗传毒性作用的研究

Toxic effect of combined exposure to formaldehyde and toluene on reproduction and heredity in male mice

目的研究甲醛和甲苯单独与联合吸入染毒致雄性昆明种小鼠的生殖毒性与遗传损伤作用,探讨其联合毒性效应。方法将108只雄性健康清洁级昆明种纯系小鼠随机分为9组,每组12只。分别为清洁空气对照组(0mg/m^3),低甲苯(500 mg/m^3)、高甲苯(2 000 mg/m^3)剂量组,低甲醛(1 mg/m^3)、低甲醛甲苯(1 mg/m^3+500 mg/m^3)、低甲醛高甲苯(1 mg/m^3+2 000 mg/m^3)剂量组,高甲醛(5 mg/m^3)、高甲醛低甲苯(5 mg/m^3+500 mg/m^3)、高甲醛甲苯(5 mg/m^3+2 000 mg/m^3)剂量组。采用静式吸入染毒,每天2 h,连续14 d。染毒结束次日每组取小鼠6只,进行骨髓细胞微核试验;于首次染毒后35 d,每组取小鼠6只,进行精子畸形试验。结果甲醛、甲苯单独及联合吸入染毒组雄性昆明种小鼠精子畸形率、骨髓细胞微核率均高于对照组。交互作用析因显示,甲醛吸入染毒可使雄性昆明种小鼠精子畸形率明显增高(F=139.66,P<0.05),甲苯染毒也可使雄性小鼠精子畸形率明显增高(F=217.11,P<0.05);甲醛染毒可使雄性小鼠骨髓细胞微核率明显增高(F=24.18,P<0.05),甲苯染毒也可使雄性小鼠骨髓细胞微核率明显增高(F=76.38,P<0.05);二者联合染毒所致的雄性小鼠精子畸形交互作用显著(F=6.14,P<0.05),但所致的雄性小鼠骨髓细胞微核交互作用尚不明显(F=0.53,P>0.05)。结论甲醛和甲苯单独与联合吸入染毒均可致小鼠精子畸形率、骨髓细胞微核率增加,联合染毒具有一定的生殖与遗传毒性协同作用。

Objective To study the toxic effect of separate and combined exposure to formaldehyde and toluene on reproduction and heredity in Kunming inbred strain male mice and discusses the joint toxic effect. Methods 108 healthy and clean Kunming inbred strain mice were randomly divided into 9 groups. The control groups were exposed at clean air,the toluene treatment groups were exposed at dosage of 500 mg / m^3,2 000 mg/m^3,the formaldehyde treatment groups were exposed at dosage of 1 mg / m^3,5 mg/m^3 and the joint treatment groups of formaldehyde and toluene were exposed at dosage of1 mg / m^3＋ 500 mg / m^3,1 mg/m^3＋ 2 000 mg / m^3,5 mg/m^3＋ 500 mg / m^3,5 mg/m^3＋ 2 000 mg / m^3 respectively. The mice were exposed to formaldehyde and toluene for 14 days,2 hours a day. On the 15 th day,6 mice from each group were used to make micronucleus tests on bone- marrow cells. On the 36 th day,the other 6 mice from each group were used to test on spermatozoa aberrations. Results The aberration rate of sperm and micronucleus rate of bone- marrow cells of the toluene treatment groups,formaldehyde treatment groups and joint groups of formaldehyde and toluene were all higher than that in control groups. As shown in the results,the aberration rates of sperm in mice were significantly higher when respectively exposed to formaldehyde（ F = 139. 66,P〈0. 05） and toluene（ F = 217. 11,P〈0. 05） and the micronucleus rate on bone- marrow cells increased greatly when respectively exposed to formaldehyde（ F = 24. 18,P〈0. 05） and toluene（ F =76. 38,P〈0. 05）. Meanwhile,there was remarkable interaction between formaldehyde and toluene in aberration rate（ F =6. 14,P〈0. 05）,but no significant interaction was found between these two substances in micronucleus rate（ F = 0. 53,P〉0. 05）. Conclusion Both separate and combined exposure to formaldehyde and toluene can cause significant increase in aberration rate of sperm and micronucleus rate of bone- marrow cells. And the joint exposure to formaldehyde and toluene has synergistic effect on reproduction and heredity in male mice.