Toxicological Sciences, Vol 50, 186-194, Copyright © 1999 by Society of Toxicology
NJ Brown-Peterson, RM Krol, Y Zhu and WE Hawkins
To investigate relationships among carcinogen exposure, cell proliferation,
and carcinogenesis, 14-day post-hatch Japanese medaka (Oryzias latipes)
were exposed to 0, 10, 25, 50, or 100 ppm N- nitrosodiethylamine (DEN) for
48 h under static renewal conditions. They were then held in clean water
until sampling at 3 and 6 months. The frequencies of hepatic lesions and
neoplasms were determined from hematoxylin/eosin-stained paraffin sections.
A significant (p < 0.0001) concentration-related increase in hepatic
vacuolated foci occurred in 3- and 6-month samples, with males having a
significantly (p = 0.02) higher incidence than females.
Concentration-related increases in degenerative lesions were documented for
spongiosis hepatis at 3 months (p = 0.053) and hepatic vacuoles at 6 months
(p = 0.005). There was a significant (p = 0.0001) concentration-related
increase in macrophage aggregates at 6 months. Basophilic foci were
significantly related (p < 0.0001) to DEN concentration at 3 months
post-exposure and were unaffected by gender or age. At both 3 and 6 months,
there were significant concentration-related increases in hepatocellular
carcinoma (p < or = 0.02). Hepatocyte proliferation in 3-month whole
specimens was quantified using an immunohistochemical assay for
proliferating- cell nuclear antigen. Trend tests and a probit dose-response
model showed a significantly positive correlation (p = 0.015) between
proliferating hepatocytes and DEN concentrations. These results confirm
that short-term exposure to low and moderate levels of DEN initiates
concentration-dependent carcinogenic effects in medaka that are apparent at
3 months postexposure. DEN could be an effective initiator in an
initiation/promotion assay for medaka using a 48-h exposure period, DEN
concentrations < or = 10 ppm, and a 6-month sampling period.
ARTICLES
N-nitrosodiethylamine initiation of carcinogenesis in Japanese medaka (Oryzias latipes): hepatocellular proliferation, toxicity, and neoplastic lesions resulting from short term, low level exposure
Department of Coastal Sciences, The University of Southern Mississippi, Ocean Springs 39566-7000, USA.
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]
|
|
|
|
 |
|
 W. E. Hawkins, W. W. Walker, J. W. Fournie, C. S. Manning, and R. M. Krol Use of the Japanese Medaka (Oryzias latipes) and Guppy (Poecilia reticulata) in Carcinogenesis Testing Under National Toxicology Program Protocols Toxicol Pathol, January 1, 2003; 31(1_suppl): 88 - 91. [Abstract] [PDF]
|
|