中华劳动卫生职业病杂志
中華勞動衛生職業病雜誌
중화노동위생직업병잡지
CHINESE JOURNAL OF INDUSTRIAL HYGIENE AND OCCUPATIONAL DISEASES
2011年
5期
324-329
,共6页
王超%刘云儒%周印%李爱萍%周建伟
王超%劉雲儒%週印%李愛萍%週建偉
왕초%류운유%주인%리애평%주건위
四氯化碳%甲醛%苯%串联重复序列%生物学标记
四氯化碳%甲醛%苯%串聯重複序列%生物學標記
사록화탄%갑철%분%천련중복서렬%생물학표기
Carbon tetrachloride%Formaldehyde%Benzene%Tandem repeat sequences%Biological markers
目的 探讨甲醛染毒致基因组扩张性简单串联重复序列(ESTR)突变小鼠的子代对外源性化学物的易感性.方法 选择经甲醛染毒小鼠繁殖的有ESTR突变的F1子代小鼠(H组)与对照组小鼠(C组),在洁净环境中饲养传代至F10代.以F5和F10代小鼠分别建立四氯化碳(CCl4)致小鼠肝脏损伤模型(CCl4处理组腹腔注射含有CCl4的橄榄油10 ml/kg,CCl4浓度分别为0.05%、0.50%和5.00%)和苯致小鼠血液毒性模型(腹腔注射苯染毒剂量分别为500、1000 mg/kg).分别测定小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活力及肝脏组织中超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量,观察肝脏组织病理学变化以评价肝氧化损伤程度;检测小鼠胸骨骨髓嗜多染红细胞微核率以评价苯的血液毒性.结果 C组F5代0.50%、5.00%CCl4染毒剂量组小鼠血清中ALT、AST活力,F10代3个CCl4染毒剂量组ALT活力和0.50%、5.00%CCl4染毒剂量组AST活力,H组F5、F10代3个CCl4染毒剂量组ALT活力和0.50%、5.00%CCl4染毒剂量组AST活力均明显高于溶剂对照组,差异均有统计学意义(P<0.05,P<0.01).与溶剂对照组比较,C组F5、F10代0.50%、5.00%CCl4染毒剂量组小鼠肝匀浆中SOD活力明显降低,F10代0.50%、5.00%CCl4染毒剂量组小鼠肝匀浆中MDA含量明显升高,差异有统计学意义(P<0.05);H组F5代0.50%、5.00%CCl4染毒剂量组,F10代5.00%CCl4染毒剂量组小鼠肝匀浆中SOD活力明显降低,F5代3个CCl4染毒剂量组,F10代0.50%、5.00%CCl4染毒剂量组小鼠肝匀浆中MDA含量明显升高,差异均有统计学意义(P<0.05).甲醛染毒后基因组ESTR突变的F5代小鼠对CCl4的相对易感性比对照组相应子代明显增加,而F10代小鼠对CCl4的相对易感性明显降低.CCl4染毒后小鼠肝脏细胞坏死和脂肪变性均呈现剂量-效应关系,而且在H组明显较C组严重.C组及H组苯染毒小鼠骨髓细胞微核率(C组500 mg/kg苯染毒组:F5代为5.88‰±4.55‰,F10代为8.25‰±2.06‰;C组1000 mg/kg苯染毒组:F5代为7.50‰±6.99‰,F10代为10.67‰±1.16‰;H组500 mg/kg苯染毒组:F5代为7.88‰±3.09‰,F10代为9.20‰±1.30‰;H组1000 mg/kg苯染毒组:F5代为9.63‰±4.34‰,F10代为13.33‰±2.08‰)随苯剂量的增加而增加,与溶剂对照组(C组F5代为1.13‰±0.35‰,F10代为1.20‰±0.82‰;H组F5代为1.25‰±0.46‰,F10代为1.33‰±1.03‰)的差异均有统计学意义(P<0.05,P<0.01).结论 甲醛暴露引起的基因组ESTR突变可改变子代小鼠对CCl4和苯的易感性.ESTR突变可能是影响机体对化学物易感性的生物学标志,其分子机制有待进一步阐明.
目的 探討甲醛染毒緻基因組擴張性簡單串聯重複序列(ESTR)突變小鼠的子代對外源性化學物的易感性.方法 選擇經甲醛染毒小鼠繁殖的有ESTR突變的F1子代小鼠(H組)與對照組小鼠(C組),在潔淨環境中飼養傳代至F10代.以F5和F10代小鼠分彆建立四氯化碳(CCl4)緻小鼠肝髒損傷模型(CCl4處理組腹腔註射含有CCl4的橄欖油10 ml/kg,CCl4濃度分彆為0.05%、0.50%和5.00%)和苯緻小鼠血液毒性模型(腹腔註射苯染毒劑量分彆為500、1000 mg/kg).分彆測定小鼠血清中丙氨痠轉氨酶(ALT)、天鼕氨痠轉氨酶(AST)活力及肝髒組織中超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量,觀察肝髒組織病理學變化以評價肝氧化損傷程度;檢測小鼠胸骨骨髓嗜多染紅細胞微覈率以評價苯的血液毒性.結果 C組F5代0.50%、5.00%CCl4染毒劑量組小鼠血清中ALT、AST活力,F10代3箇CCl4染毒劑量組ALT活力和0.50%、5.00%CCl4染毒劑量組AST活力,H組F5、F10代3箇CCl4染毒劑量組ALT活力和0.50%、5.00%CCl4染毒劑量組AST活力均明顯高于溶劑對照組,差異均有統計學意義(P<0.05,P<0.01).與溶劑對照組比較,C組F5、F10代0.50%、5.00%CCl4染毒劑量組小鼠肝勻漿中SOD活力明顯降低,F10代0.50%、5.00%CCl4染毒劑量組小鼠肝勻漿中MDA含量明顯升高,差異有統計學意義(P<0.05);H組F5代0.50%、5.00%CCl4染毒劑量組,F10代5.00%CCl4染毒劑量組小鼠肝勻漿中SOD活力明顯降低,F5代3箇CCl4染毒劑量組,F10代0.50%、5.00%CCl4染毒劑量組小鼠肝勻漿中MDA含量明顯升高,差異均有統計學意義(P<0.05).甲醛染毒後基因組ESTR突變的F5代小鼠對CCl4的相對易感性比對照組相應子代明顯增加,而F10代小鼠對CCl4的相對易感性明顯降低.CCl4染毒後小鼠肝髒細胞壞死和脂肪變性均呈現劑量-效應關繫,而且在H組明顯較C組嚴重.C組及H組苯染毒小鼠骨髓細胞微覈率(C組500 mg/kg苯染毒組:F5代為5.88‰±4.55‰,F10代為8.25‰±2.06‰;C組1000 mg/kg苯染毒組:F5代為7.50‰±6.99‰,F10代為10.67‰±1.16‰;H組500 mg/kg苯染毒組:F5代為7.88‰±3.09‰,F10代為9.20‰±1.30‰;H組1000 mg/kg苯染毒組:F5代為9.63‰±4.34‰,F10代為13.33‰±2.08‰)隨苯劑量的增加而增加,與溶劑對照組(C組F5代為1.13‰±0.35‰,F10代為1.20‰±0.82‰;H組F5代為1.25‰±0.46‰,F10代為1.33‰±1.03‰)的差異均有統計學意義(P<0.05,P<0.01).結論 甲醛暴露引起的基因組ESTR突變可改變子代小鼠對CCl4和苯的易感性.ESTR突變可能是影響機體對化學物易感性的生物學標誌,其分子機製有待進一步闡明.
목적 탐토갑철염독치기인조확장성간단천련중복서렬(ESTR)돌변소서적자대대외원성화학물적역감성.방법 선택경갑철염독소서번식적유ESTR돌변적F1자대소서(H조)여대조조소서(C조),재길정배경중사양전대지F10대.이F5화F10대소서분별건립사록화탄(CCl4)치소서간장손상모형(CCl4처리조복강주사함유CCl4적감람유10 ml/kg,CCl4농도분별위0.05%、0.50%화5.00%)화분치소서혈액독성모형(복강주사분염독제량분별위500、1000 mg/kg).분별측정소서혈청중병안산전안매(ALT)、천동안산전안매(AST)활력급간장조직중초양화물기화매(SOD)활력、병이철(MDA)함량,관찰간장조직병이학변화이평개간양화손상정도;검측소서흉골골수기다염홍세포미핵솔이평개분적혈액독성.결과 C조F5대0.50%、5.00%CCl4염독제량조소서혈청중ALT、AST활력,F10대3개CCl4염독제량조ALT활력화0.50%、5.00%CCl4염독제량조AST활력,H조F5、F10대3개CCl4염독제량조ALT활력화0.50%、5.00%CCl4염독제량조AST활력균명현고우용제대조조,차이균유통계학의의(P<0.05,P<0.01).여용제대조조비교,C조F5、F10대0.50%、5.00%CCl4염독제량조소서간균장중SOD활력명현강저,F10대0.50%、5.00%CCl4염독제량조소서간균장중MDA함량명현승고,차이유통계학의의(P<0.05);H조F5대0.50%、5.00%CCl4염독제량조,F10대5.00%CCl4염독제량조소서간균장중SOD활력명현강저,F5대3개CCl4염독제량조,F10대0.50%、5.00%CCl4염독제량조소서간균장중MDA함량명현승고,차이균유통계학의의(P<0.05).갑철염독후기인조ESTR돌변적F5대소서대CCl4적상대역감성비대조조상응자대명현증가,이F10대소서대CCl4적상대역감성명현강저.CCl4염독후소서간장세포배사화지방변성균정현제량-효응관계,이차재H조명현교C조엄중.C조급H조분염독소서골수세포미핵솔(C조500 mg/kg분염독조:F5대위5.88‰±4.55‰,F10대위8.25‰±2.06‰;C조1000 mg/kg분염독조:F5대위7.50‰±6.99‰,F10대위10.67‰±1.16‰;H조500 mg/kg분염독조:F5대위7.88‰±3.09‰,F10대위9.20‰±1.30‰;H조1000 mg/kg분염독조:F5대위9.63‰±4.34‰,F10대위13.33‰±2.08‰)수분제량적증가이증가,여용제대조조(C조F5대위1.13‰±0.35‰,F10대위1.20‰±0.82‰;H조F5대위1.25‰±0.46‰,F10대위1.33‰±1.03‰)적차이균유통계학의의(P<0.05,P<0.01).결론 갑철폭로인기적기인조ESTR돌변가개변자대소서대CCl4화분적역감성.ESTR돌변가능시영향궤체대화학물역감성적생물학표지,기분자궤제유대진일보천명.
Objective To investigate the susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats (ESTR) mutation mice exposed to formaldehyde (FA). Methods F5 and F10 offspring (200 mg/m3 ×2 hours) served as H group and ICR mice were used as control group(group C). The F5 and F10 offspring were exposed to 10 ml/kg carbon tetrachloride at the doses of 0.05%, 0.50% or 5.00% for 24 hours, respectively or 500 or 1000 mg/kg benzene for 24 hours, respectively by intraperitoneal injection. Serum alanine transaminase (ALT), aspartate transaminase (AST) and the hepatic superoxide dismutase (SOD) or malondialdehyde (MDA) were detected; also the hepatic pathological changes were observed under light microscope; the micronucleus in sternum bone marrow cells as the biomarker of benzene blood toxicity were measured. Results ALT and AST activities in group C of F5 mice exposed to 0.50% and 5.00% CCl4, ALT in groups C and H of F10 mice exposed to 0.05%, 0.50%, 5.00% CCl4, AST in groups C and H of F10 mice exposed to 0.50% and 5.00% CCl4 were significantly higher than those in controls, respectively (P<0.05); as compared to the control, hepatic SOD activities in group C of F5 and F10 mice exposed to 0.50% and 5.00% CCl4, in group H of F5 mice exposed to 0.50% and 5.00% CCl4, and F10 mice exposed to 5.00% CCl4 were significantly reduced, respectively (P<0.05); however, MDA contents in group C of F10 mice exposed to 0.50% and 5.00% CCl4, in group H of F5 mice exposed to 0.05% and 0.50%, 5.00% CCl4 and F10 mice exposed to 0.50% and 5.00% CCl4 were significantly increased than those in control group, respectively (P<0.05). The susceptibility to CCl4 in ESTR mutation F5 mice exposed to FA was significantly higher than that in control F5 mice, but the susceptibility to CCl4 in ESTR mutation F10 mice exposed to FA was significantly lower than that in control F10 mice. The histopathological examination showed that the injury of hepatocytes in C and H groups significantly increased CCl4 doses, and the injury of hepatocytes in H group was higher than that in C group. The micronuclear rates in C and H group mice exposed to benzene (500 mg/kg C group, F5 and F10 mice; 1000 mg/kg C group, F5 and F10 mice; 500 mg/kg H group, F5 and F10 mice; 1000 mg/kg C group, F5 and F10 mice) were 5.88‰±4.55‰, 8.25‰±2.06‰, 7.50‰±6.99‰, 10.67‰±1.16‰, 7.88v±3.09‰, 9.20‰±1.30‰, 9.63‰±4.34‰ and 13.33‰±2.08‰, respectively, which were significantly higher than those (1.13‰±0.35‰, 1.20‰±0.82‰, 1.25‰±0.46‰, 1.33‰±1.03‰) in the solvent control group(P<0.05 or P<0.01). Conclusion FA could result in the change of susceptibility to CCl4 and benzene in offspring of ESTR mutation mice. ESTR mutation may be a biomarker of the susceptibility to chemicals, but the molecular mechanisms should be investigated in the future.
