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Modulation of N-methyl-N'-nitro-nitrosoguanidine multiorgan carcinogenesis by dehydroepiandrosterone in rainbow trout.

Abstract：

:Dehydroepiandrosterone (DHEA) and its sulfate conjugate are the major circulating steroids in human plasma. Low levels of these adrenal steroids are associated with a number of human diseases including certain cancers. In animal studies, DHEA is chemopreventive toward both spontaneous and chemically induced cancers. A potential concern for long-term usage of DHEA in humans is the finding that DHEA is hepatocarcinogenic in rats. The human health risk has been thought to be minimal, however, as the mechanism of DHEA hepatocarcinogenesis is assumed to be due to its properties as a peroxisome proliferator, a class of compounds to which humans are relatively insensitive. Recently, we have found DHEA to be a potent promoter of aflatoxin B1-initiation as well as a complete hepatocarcinogen in the rainbow trout, a species which is also insensitive to peroxisome proliferators. In order to determine the initiator- and tissue-specificity of DHEA promotion, we examined the effects of DHEA on N-methyl-N'-nitro-nitrosoguanidine (MNNG)-initiated carcinogenesis. Trout fry were initiated by a bath exposure (30 min at 35 ppm) to MNNG and then fed DHEA at levels of 0, 55, 111, 222, 444, or 888 ppm for 7 months. DHEA increased liver tumor incidence, multiplicity, and size in a dose-dependent manner. The liver tumor incidence ranged from 0 in the MNNG-initiated controls to 99% in initiated trout fed 888 ppm DHEA. The latter represents a potential synergistic interaction in liver between MNNG and DHEA, as tumor incidence in sham-initiated trout fed this level of DHEA was 41%. The kidney tumor incidence was also enhanced two- and threefold over initiated controls by 111 and 888 ppm DHEA, respectively. In contrast, the total number of stomach and swim bladder tumors was reduced by DHEA treatment. This study demonstrates differential effects of DHEA on MNNG-initiated carcinogenesis in liver, kidney, stomach, and swim bladder.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Orner GA,Hendricks JD,Arbogast D,Williams DE

doi

10.1006/taap.1996.0321

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

548-54

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(96)90321-X

journal_volume

141

pub_type

杂志文章

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Modulation of N-methyl-N'-nitro-nitrosoguanidine multiorgan carcinogenesis by dehydroepiandrosterone in rainbow trout.