Carcinogenesis, Vol 19, 1855-1862, Copyright © 1998 by Oxford University Press
RS Thomas, DL Gustafson, WA Pott, ME Long, SA Benjamin and RS Yang
Pentachlorobenzene (PeCB) is an important environmental contaminant derived
primarily from the by-product contamination of the popular fungicides
hexachlorobenzene and pentachloronitrobenzene. Its tumor- promoting
activity was studied in a medium-term initiation/promotion assay in male
F344 rats. Animals were given a single i.p. injection of diethylnitrosamine
(200 mg/kg body weight) and 2 weeks later were administered 0.1 or 0.4
mmol/kg per day PeCB by gavage in a corn oil vehicle, 7 days/week. At the
end of week 3, rats were subjected to a partial hepatectomy. Results showed
that PeCB, at both doses, significantly increased both the number and area
of glutathione S- transferase pi (GST-P) foci (>0.2 mm diameter) (P <
0.05). This trend was dose-dependent. In addition to increases in
preneoplastic foci, liver glutathione concentrations and
glutathione-associated enzymes showed significant changes in animals
treated with PeCB. Glutathione reductase (GR) and gamma-glutamylcysteine
synthetase (gamma-GCS) were both significantly induced in the centrilobular
region. Changes in oxidized glutathione concentrations corresponded with
the increase in GR activity with decreases of 40 and 30% in the low and
high dose groups, respectively. No significant changes were detected in
reduced glutathione concentrations. Together with changes in GR and
gamma-GCS expression, a decrease in GST-P foci around the central veins was
significant (P = 0.004) at the high dose. In these animals, 26% of the foci
were classified as centrilobular whereas 37 and 39% of the foci were
centrilobular in the low dose and control groups, respectively. Because of
the co-localized nature of the changes in glutathione- associated enzymes
and the decreased incidence of centrilobular foci, our results suggest that
the reduced cellular environment may ultimately play a role in negatively
selecting for foci growth.
ARTICLES
Evidence for hepatocarcinogenic activity of pentachlorobenzene with intralobular variation in foci incidence
Center for Environmental Toxicology and Technology, Department of Environmental Health, Colorado State University, Fort Collins 80523- 1680, USA. thomas@oncology.wisc.edu
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