Document Detail


Organ-specific and transplacental DNA damage and its repair in rats treated with 1,2-dibromo-3-chloropropane.
MedLine Citation:
PMID:  8665617     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An in vivo genotoxicity assay system based on alkaline elution has been used to study the formation and removal of DNA damage induced by 1,2-dibromo-3-chloropropane (DBCP). Cells/nuclei from different tissues and organs of Wistar rats were prepared by a rapid mincing/homogenization technique. Thirty-six samples of which up to 11 were from different organs of the same animal, were then assayed in parallel for DNA damage (DNA single-strand breaks plus alkali-labile sites = SSBs) with a semi-automated alkaline elution system. A single i.p. injection of DBCP gave dose-(5 and 10 mg/kg) and time-(20 min-4 h) dependent SSBs in kidney and liver DNA from male rats. At 10 mg/kg DBCP, SSBs were formed in all organs examined except the bone marrow and colon; however, an increased dose of 40 mg/kg produced SSBs also in the latter two organs. The relative susceptibilities to DBCP-induced DNA damage were: kidney approximately duodenum > liver > lung approximately brain approximately urinary bladder approximately glandular stomach > spleen approximately testis > bone marrow approximately colon. These relative levels correlate with previous data on tissue distribution and organ necrosis in liver, kidney and testis of rats given a single i.p. dose of DBCP. When female rats were injected i.p. with 5, 10 or 20 mg/kg (nonhepatotoxic doses) at day 20 of pregnancy, similar levels of SSBs were detected in the livers of the dam and the fetuses. In adult male rats, time-dependent changes in SSBs were followed in the liver and kidney after DBCP exposure. In both organs SSBs peaked around 4 h post-exposure, 50% had been removed by 12-24 h, whereas at day 2-3 SSB frequencies had returned to control levels. Pretreatment of rats with phenobarbital prior to DBCP exposure reduced the maximum level of DNA damage as well as its persistence. In cultured primary hepatocytes from male rats exposed in vitro to DBCP (2-20 microM. 1 h), 50% of the initial DNA damage had been repaired within approximately 100 min. In conclusion, the experiments indicate that the distribution characteristics of DBCP are of major importance for DNA damage and its persistence in various organs of rats. The data are also in accordance with glutathione-S-transferase, rather than P450, being the most important pathway for metabolic activation of DBCP in rat extrahepatic tissues including the fetal liver. It appears that alkaline elution of cells/nuclei prepared from exposed animals constitutes a sensitive, rapid and versatile technique to study organ- and cell-specific genotoxicity in vivo.
Authors:
G Brunborg; E J Søderlund; J A Holme; E Dybing
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  101     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-08-02     Completed Date:  1996-08-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  33-48     Citation Subset:  IM    
Affiliation:
National Institute of Public Health, Department of Environmental Medicine, Oslo, Norway.
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA / drug effects
DNA Damage*
DNA Repair*
Female
Insecticides / pharmacology*
Male
Maternal-Fetal Exchange*
Organ Specificity*
Pregnancy
Propane / analogs & derivatives*,  pharmacology
Rats
Rats, Wistar
Grant Support
ID/Acronym/Agency:
ES 02728/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Insecticides; 74-98-6/Propane; 9007-49-2/DNA; 96-12-8/1,2-dibromo-3-chloropropane

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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