Carcinogenesis, Vol 19, 515-518, Copyright © 1998 by Oxford University Press
JM Law, M Bull, J Nakamura and JA Swenberg
Small fish models are being used with increasing frequency for
carcinogenicity testing and comparative cancer research in the US, Canada
and Europe. However, there is a need to further define the early
biochemical events of carcinogenesis in these species. Identification and
quantitation of DNA adducts can integrate all of the various factors
involved in chemical exposure, uptake, distribution and biotransformation
of a putative carcinogen. In the present study, Japanese medaka (Oryzias
latipes) were exposed to the alkylating agent, diethylnitrosamine (DEN), in
the ambient water. Liver DNA was analyzed for O6-ethylguanine (O6EG),
O4-ethylthymidine (O4ET) and O2- ethylthymidine (O2ET) by the
immuno-slot-blot technique, using monoclonal antibodies against each adduct
of interest. While fish exposed to 10 p.p.m. DEN had liver DNA adduct
concentrations at or only slightly higher than background levels, those
exposed to 100 p.p.m. DEN averaged 34 and 53 pmol O6EG/micromol guanine, 15
and 41 pmol O2ET/micromol thymidine and 2 and 6 pmol O4ET/micromol
thymidine at 0 and 24 h post-exposure, respectively. The results of this
study show that, under these short-term exposure conditions, ethyl-DNA
adducts appear to accumulate in medaka liver tissue in a sublinear (i.e.
non- linear) fashion after aqueous exposure to DEN. Thus, critical DNA
repair enzymes such as O6-alkylguanine DNA alkyltransferase, which are
relatively efficient at lower carcinogen levels, are probably saturated at
the 100 p.p.m. concentration level of DEN.
ARTICLES
Molecular dosimetry of DNA adducts in the medaka small fish model
Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA. MAC_LAW@NCSU.EDU
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. E. Kissling, N. J. Bernheim, W. E. Hawkins, M. J. Wolfe, M. P. Jokinen, C. S. Smith, R. A. Herbert, and G. A. Boorman The Utility of the Guppy (Poecilia reticulata) and Medaka (Oryzias latipes) in Evaluation of Chemicals for Carcinogenicity Toxicol. Sci., July 1, 2006; 92(1): 143 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Brennan, E. M. Boncavage-Hennessey, M. J. Wolfe, M. W. Toussaint, W. E. Dennis, A. B. Rosencrance, and H. S. Gardner JR An In Vivo Method for Using 5-Bromo-2'-deoxyuridine (BrdU) as a Marker of Chemically-Induced Hepatocellular Proliferation in the Japanese Medaka (Oryzias latipes) Toxicol Pathol, April 1, 2001; 29(3): 387 - 397. [Abstract] [PDF]
|
|
|
|
|
|
M. W. Toussaint, M. J. Wolfe, D. T. Burton, F. J. Hoffmann, T. R. Shedd, and H. S. Gardner JR Histopathology of Japanese Medaka (Oryzias latipes) Chronically Exposed to a Complex Environmental Mixture Toxicol Pathol, November 1, 1999; 27(6): 652 - 663. [Abstract] [PDF]
|
|