The Study Of Immunotoxicity Of Benzene On Mother Generation And Offspring Mice

Objective:To investigate the effect of benzene(BZ) on immune toxicity injury in mother geneartion and offspring mice,and provide scientific evidence for overall assessing its reproductive and developmental toxicity further.Method:40 Kunming fetation mice were divided randomly into 4 groups. From pregnanted after 7days, each of group was intaked benzene vapour(0.0,5.0,10.0 and15.0mg/m3 respectively, 2 hour/day) untill to put to death. In 1 day and 7days after parturition,5 mother generation mice and 5 offspring mice were killed in each group and blood was collected,the serum and lymph-cell was separated for detecting immunoglobulin, IL-2,IL-4,INF-γ,lymphocyte subsets, the thymus and spleen were extracted for calculating organic coefficient. 1/2 spleen of each mouse was used for pathology observation and the other for determining these index ,such as NK cytoactive, proliferative ability of splenic lymphocyte, cell cycle and apoptosis.Results:1. During the time of using narcotics in mother mice, of which action and appetite have no change. clothing hair gloss, no phenomenon of death and intoxation. in 6,9,12,15 days after poisoned, the body weight of mother mice in middle and high concentration benzene groups were lower than air control group(P<0.05), the birth weight of offspring mice in middle and high concentration benzene groups lower than air control group in postnatal 7days (P<0.05), and show concentration-dependent relation. Offspring mice in 3 poisoned groups could observe abnormity in some degree, such as micromelia, bobtail, cleft palate.and the rate of teratogeny was higher than air control group(P<0.05).2. The 1day and 7days after parturition, the spleen coefficient of mother mice in high concentration BZ group was lower than control group (P <0.05), while the thymus coefficient show no significant difference statistically comparing with control group (P>0.05). The spleen and thymus coefficient of offspring mice in middle and high concentration benzene groups were lower than air control group in postnatal 1day and 7days (P<0.05). The noduli lymphatici lienales of mother mice in poisoned groups was tiny and few, depauperat white pulp, vague germinal center and marginal zone, erythrocytosis, sinus lienis engorgement, white pulp and red pulp have no obvious outer limits.3. BZ could degrade NK cytoactive and proliferative ability of splenic lymphocyte in mother or offspring mice. The 1day and 7days after parturition, the NK cytoactive of mother mice in BZ groups were lower than control group(P <0.05), and there was a dose-response relationship. The NK cytoactive and proliferative ability of splenic lymphocyte of offspring mice in middle and high concentration benzene groups were lower than air control group in postnatal 1day and 7days(P<0.05).4. The spleen lymph-cell of offspring mice in middle and high concentration benzene groups were higher than control group in'G0/G1'and'G2+M'period(P<0.05), while lower than control group in'S'period(P<0.05). The rate of spleen lymph-cells apoptosis in BZ groups was higher than control group(P<0.05) and showed obvious concentration-response relationship.5. During the sensitive period of fetation, BZ was intaked by mother mice.show that the function of phagocytosis of enterocoelia macrophages and the Red Cell Immune Adherence Function degraded in offspring mice of BZ groups, comparing with control group, there was significantly difference (P <0.05).6. The 1day and 7days after parturition, BZ with middle and high concentration could degrade the rate of CD3+,CD4+(P<0.01), CD4+/CD8+(P<0.01) in mother generation and offspring mice.The degression degree of the rate of CD3+,CD4+and CD4+/CD8+ was related with the administrated concentration of BZ(P<0.05), and there was obvious dose-response relationship.7. BZ with different concentration could reduce the serum immune globulin (IgM,IgG,IgA) in mother generation and offspring mice in1day and 7days after parturition, the serum immune globulin(IgM, IgG,IgA) in middle and high concentration benzene groups were lower than control group(P<0.05) and showed obvious dose-response relationship. 8. During the sensitive period of fetation, BZ was intaked by mother mice, show that IL-2,IL-4 and INF-γof offspring mice in middle and high concentration benzene groups were lower than control group(P<0.05) in 1 day and 7days after birth.but there was no significantly difference between the offspring mice in 1 day and 7days after birth(P>0.05).Conclusion:Through inhalation of BZ by mother mice in the sensitive period of fetation, show that benzene can inhibit embryonic development in vivo, lead to embryonic malformation or dead embryo .It also can restrain the immune function(cell immunity, humoral immunity, immune molecule et al) of mother generation and offspring mice.