Application of rat medium-term bioassays for detecting carcinogenic
and modifying potentials of endocrine active substances
K. Imaida, S. Tamano, A. Hagiwara, S. Fukushima, T. Shirai, and N.
Ito
Faculty of Medicine, Kagawa Medical University, 1750-1
Ikenobe, Miki cho, Kitagun, Kagawa 761-0793, Japan;
Daiyu-kai Institute of Medical Sciences, 64 Gura, Nishiazai, Azai-cho,
Ichinomiya 491-0113, Japan;
Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka
545-8585, Japan;
Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi,
Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan;
Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku,
Nagoya, 467-8601, Japan
Abstract: Two in vivo bioassay methods, a rat medium-term liver
bioassay and a rat multiorgan bioassay, can be used for detecting carcinogenic
or modifying potentials of endocrine active substances (EASs) on endocrine
disruption (ED). The first bioassay, the rat mediumterm liver bioassay,
is fundamentally based on the two-step hypothesis of liver carcinogenesis;
initiation with diethylnitrosamine (DEN, 200 mg/kg b.w., ip) is followed
by test chemical administrations during the second stage, in combination
with 2/3 partial hepatectomy. It requires only eight weeks for animal
experimental treatment and a further few weeks for quantitative analysis
of immunohistochemically demonstrated gluthathione-S-transeferase
placental form positive hepatic foci. A total of 313 chemicals/substances
have already been analyzed, and the efficacy of the system for hepatocarcinogenesis
has thereby been well established. This bioassay also provides information
concerning dose responses and inhibitory potentials of test chemicals.
Several possible EASs, most of them categorized as pesticides, have
already been examined in this bioassay, and dose-response studies of
nonylphenol, bisphenol A, and styrene have also been tested. Another
bioassay, a medium-term, multiorgan bioassay system, using five different
chemical carcinogens -DEN, MNU, BBN, DMH, and DHPN- has also been established
for rapid detection of not only hepatocarcinogens, but also other organ-targeted
carcinogens. These medium-term bioassays are particularly useful and
reliable methods for detecting carcinogenic or modifying potentials
of low doses of test chemicals, such as EASs, and these methods can
be used for the effects of chemical mixtures of EASs.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.