In vivo genotoxicity and acute hepatotoxicity of 1,2-dichloroethane in mice: comparison of oral, intraperitoneal, and inhalation routes of exposure.
In vivo genotoxicity and acute hepatotoxicity of 1,2-dichloroethane in mice: comparison of oral, intraperitoneal, and inhalation routes of exposure.
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DOI：
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发表时间：
1984-10
期刊：
影响因子：
11.2
通讯作者：
R. Storer;N. M. Jackson;R. Conolly
中科院分区：
文献类型：
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作者：
R. Storer;N. M. Jackson;R. Conolly
在雄性C57 BL/6 X C3 H F1（以下称为B6 C3 F1）小鼠肝脏中研究了1，2-二氯乙烷（DCE）单次经口给药后的体内遗传毒性，腹腔注射，和吸入暴露。还检查了DCE的急性肝毒性，以确定每种给药途径的非致坏死性暴露水平。经口给药后4小时，通过碱性DNA解旋/羟基磷灰石色谱法在肝DNA中证实单链断裂和/或碱不稳定性病变。或i. p.给药非致坏死剂量（100 mg/kg，p.o.; 150 mg/kg，i.p.）给四到六只小鼠的组。小鼠吸入非致坏死（150 ppm）或致坏死（500 ppm）浓度的DCE 4小时后，未立即发现肝DNA损伤的证据。将小鼠吸入暴露于24小时内导致高死亡率的DCE浓度（1000至2000 ppm）4小时，在4小时时产生肝DNA损伤的证据，但不能排除这种损伤是由于暴露的急性坏死效应造成的可能性。腹腔注射DCE（200 mg/kg）后4小时观察到的肝DNA损伤的显著部分在24小时后仍然明显，表明DNA中未修复的损伤持续存在。这些发现与两项长期致癌性生物测定的看似矛盾的结果一致，其中发现DCE在灌胃给药时对Osdel-Mendel大鼠和B6 C3 F1小鼠具有致癌性，但在长期吸入暴露后对Sprague-Dawley大鼠和Swiss小鼠无致瘤性。因此，我们的研究结果为DCE体内遗传毒性和致癌性中给药途径效应的重要性提供了额外的证据。
The in vivo genotoxicity of 1,2-dichloroethane (DCE) was studied in the liver of male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice after single p.o., i.p., and inhalation exposures. The acute hepatotoxicity of DCE was also examined in order to determine nonnecrogenic exposure levels for each route of administration. Single-strand breaks and/or alkali-labile lesions were demonstrated by alkaline DNA-unwinding/hydroxylapatite chromatography in hepatic DNA at 4 hr after p.o. or i.p. administration of nonnecrogenic doses (100 mg/kg, p.o.; 150 mg/kg, i.p.) of DCE to groups of four to six mice. No evidence of hepatic DNA damage was found immediately following 4-hr inhalation exposures of mice to a nonnecrogenic (150 ppm) or necrogenic (500 ppm) concentration of DCE. Four-hr inhalation exposures of mice to concentrations of DCE causing high mortality within 24 hr (1000 to 2000 ppm) produced evidence of hepatic DNA damage at 4 hr, but the possibility that this damage was due to the acute necrogenic effects of the exposures could not be excluded. A significant fraction of the hepatic DNA damage observed 4 hr after i.p. administration of DCE (200 mg/kg) was still evident after 24 hr, indicating the persistence of unrepaired lesions in the DNA. These findings are consistent with the seemingly contradictory results of the two long-term carcinogenicity bioassays, in which DCE was found to be carcinogenic to Osborne-Mendel rats and B6C3F1, mice when administered by gavage but nontumorigenic to Sprague-Dawley rats and Swiss mice after chronic inhalation exposure. Therefore, our results provide additional evidence for the importance of a route of administration effect in the in vivo genotoxicity and carcinogenicity of DCE.