Carcinogenesis, Vol 19, 161-167, Copyright © 1998 by Oxford University Press
GA Orner, JD Hendricks, D Arbogast and DE Williams
Previously, we demonstrated that dehydroepiandrosterone (DHEA) enhances
aflatoxin B1 (AFB1) hepatocarcinogenesis in trout when administered
following AFB1 exposure. This paper examines the effect of DHEA on tumor
latency and the comparative potency for DHEA to modulate AFB1
carcinogenesis when administered prior to and concurrent with AFB1 compared
with a post-initiation exposure. Trout were initiated by a 30 min water
bath exposure to 10 p.p.b. AFB1. At 3 months post-initiation, animals were
started on either control diet or a diet containing 444 p.p.m.
dehydroepiandrosterone (DHEA). Fifty trout per treatment were sampled prior
to the start of experimental diets, and then at monthly intervals for the
next 7 months and examined for the presence of tumors. Tumors were not
detected in initiated controls until 7 months after initiation. In
initiated trout fed DHEA, the first tumor was detected 5 months after
initiation (after just 2 months of dietary DHEA). At 6 months
post-initiation, 20% of the AFB1-initiated trout fed DHEA had tumors, while
no tumors were visible in either AFB1-initiated controls or noninitiated
trout fed DHEA. A second experiment was designed to determine if the
enhancing effect of DHEA on AFB1 carcinogenesis is dependent on the time of
DHEA administration relative to the time of AFB1 exposure, and if DHEA
could be chemopreventive if administered prior to and concurrent with AFB1.
Trout were fed one of two levels of DHEA (888 or 1776 p.p.m.) either prior
to and during a 4- week initiation period of dietary AFB1 administration,
or for 8 weeks following initiation with AFB1. At 9 months after initiation
the livers were examined for tumors. Neither exposure protocol provided
protection towards AFB1 hepatocarcinogenesis. The strongest enhancement
occurred when DHEA was fed during the post-initiation period. Levels of p53
and p34cdc2 were decreased by DHEA treatment, indicating that DHEA may act
through alterations in cell-cycle control.
ARTICLES
Modulation of aflatoxin-B1 hepatocarcinogenesis in trout by dehydroepiandrosterone: initiation/post-initiation and latency effects
Toxicology Program, Oregon State University, Corvallis 97331-6602, USA.
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