Skip Navigation


ToxSci Advance Access originally published online on July 11, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
75/2/321    most recent
kfg186v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Faiola, B.
Right arrow Articles by Recio, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Faiola, B.
Right arrow Articles by Recio, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 75, 321-332 (2003)
Copyright © 2003 by the Society of Toxicology

GENETIC TOXICOLOGY

Variations in Prkdc and Susceptibility to Benzene-Induced Toxicity in Mice

Brenda Faiola1, Alison K. Bauer2, Elizabeth S. Fuller3, Victoria A. Wong, Linda J. Pluta, Diane J. Abernethy, James B. Mangum, Jeffrey I. Everitt4 and Leslie Recio5

CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709

ABSTRACT

Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), encoded by Prkdc, is one such protein. DNA-PKcs is involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here we compared the toxic effects of benzene on mice (C57BL/6 and 129/Sv) homozygous for the wild-type Prkdc allele and mice (129/SvJ) homozygous for a Prkdc functional polymorphism that leads to diminished DNA-PK activity and enhanced apoptosis in response to radiation-induced damage. Male and female mice were exposed to 0, 10, 50, or 100 ppm benzene for 6 h/d, 5 d/week for 2 weeks. Male mice were more susceptible to benzene toxicity compared with females. Hematotoxicity was evident in all male mice but was not seen in female mice. We observed similar, large increases in both micronucleated erythrocyte populations in all male mice. Female mice had smaller but significant increases in micronucleated cells. The p53-dependent response was induced in all strains and genders of mice following benzene exposure, as indicated by an increase in p21 mRNA levels in bone marrow that frequently corresponded with cell cycle arrest in G2/M. Prkdc does not appear to be a significant genetic susceptibility factor for acute benzene toxicity. Moreover, the role of NHEJ, mediated by DNA-PK, in restoring genomic integrity following benzene-induced DSB remains equivocal.

Key Words: DNA-PKcs; Prkdc; benzene; nonhomologous end-joining; susceptibility; toxicity.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Exp ToxicolHome page
H. Ahmad Khan
Short Review: Benzene's toxicity: a consolidated short review of human and animal studies
Human and Experimental Toxicology, September 1, 2007; 26(9): 677 - 685.
[Abstract] [PDF]

Home page
 Stem CellsHome page
B. Faiola, E. S. Fuller, V. A. Wong, L. Pluta, D. J. Abernethy, J. Rose, and L. Recio
Exposure of Hematopoietic Stem Cells to Benzene or 1,4-Benzoquinone Induces Gender-Specific Gene Expression
Stem Cells, September 1, 2004; 22(5): 750 - 758.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
D. J. Abernethy, E. V. Kleymenova, J. Rose, L. Recio, and B. Faiola
Human CD34+ Hematopoietic Progenitor Cells Are Sensitive Targets for Toxicity Induced by 1,4-Benzoquinone
Toxicol. Sci., May 1, 2004; 79(1): 82 - 89.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.