Abstract:
:The covalent binding of 14C-1,1,2-trichloroethylene (14C-TRI) metabolites to calf thymus DNA in vitro and to RNA and DNA of mouse brain, lung, liver, kidney, spleen, pancreas, and testis after repeated i.p. injections has been studied. Hydrolysates of DNA reacted with 14C-TRI in vitro and hydrolysates of RNA and DNA from selected organs were separated on Aminex A6 for quantitation of alkylation products. The presence of 3,N4-etheno(deoxy)cytidine, 1,N6-etheno(deoxy)adenosine and 1,N6-ethenoadenine was investigated. No radioactivity could be registered in DNA incubated with 14C-TRI in the absence of liver microsomes. Covalent binding of 14C-TRI to DNA took place in the presence of liver microsomes from control mice. The binding was enhanced by 50% if liver microsomes from phenobarbital pretreated mice were used. The radioactivity in DNA reacted with 14C-TRI and microsomes from control mice was eluted in early fractions and together with thymidine. The same two peaks appeared on chromatography of DNA incubated with 14C-TRI and liver microsomes from phenobarbital pretreated mice. In addition, radioactivity was eluted together with 1,N6-ethenoadenine. Radioactivity was registered in RNA and DNA from all of the studied organs after i.p. injections of 14C-TRI. The radioactivity in RNA increased in the order brain less than testis less than pancreas less than kidney less than liver less than lung less than spleen. The radioactivity in DNA increased in the order brain less than kidney less than testis less than lung less than pancreas less than liver less than spleen. Aminex A6 chromatography revealed that the entire radioactivity in RNA from liver and kidney and in DNA from kidney, testis, lung, pancreas, and spleen was due to metabolic incorporation, particularly into guanine and adenine. This finding indicates that the C-C bond in TRI is split, with the formation of C1-fragments, during biotransformation in vivo. In liver DNA, the metabolic incorporation of radioactivity was insignificant. Instead, the dominant part of the radioactivity in liver DNA was eluted in early fractions. The elution profile of radioactivity in liver DNA gave no direct evidence of the formation of TRI-DNA adducts in vivo. No etheno-derivatives were identified as alkylation products of TRI in vivo, which is consistent with current theories of the metabolic fate of TRI.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Bergman Kdoi
10.1007/BF01239202subject
Has Abstractpub_date
1983-11-01 00:00:00pages
181-93issue
3eissn
0340-5761issn
1432-0738journal_volume
54pub_type
杂志文章abstract::The OECD has developed an "enhanced Test Guideline 407" (TG 407) protocol for detecting endocrine effects during the course of a 28-day testing scheme. This protocol has gone through a validation process with (anti)estrogenic and (anti)androgenic compounds and substances that affect the thyroid (thyroxine and propylth...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
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journal_title:Archives of toxicology
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journal_title:Archives of toxicology
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journal_title:Archives of toxicology
pub_type: 杂志文章
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更新日期:1987-08-01 00:00:00
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pub_type: 杂志文章
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01974011
更新日期:1992-01-01 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00310329
更新日期:1978-08-09 00:00:00
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journal_title:Archives of toxicology
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pub_type: 杂志文章
doi:10.1007/BF00296900
更新日期:1979-02-23 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00296978
更新日期:1987-01-01 00:00:00
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更新日期:2001-09-01 00:00:00
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更新日期:2017-05-01 00:00:00
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journal_title:Archives of toxicology
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更新日期:2012-03-01 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
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更新日期:1983-10-01 00:00:00
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journal_title:Archives of toxicology
pub_type: 杂志文章
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更新日期:1991-01-01 00:00:00
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journal_title:Archives of toxicology
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更新日期:1996-01-01 00:00:00
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更新日期:2003-06-01 00:00:00